Identification of T-cell Receptors Targeting KRAS-Mutated Human Tumors
Open accessPublished version of a preprint
Abstract
KRAS is one of the most frequently mutated proto-oncogenes in human cancers. The dominant oncogenic mutations of KRAS are single amino acid substitutions at codon 12, in particular G12D and G12V present in 60% to 70% of pancreatic cancers and 20% to 30% of colorectal cancers. The consistency, frequency, and tumor specificity of these “neoantigens” make them attractive therapeutic targets. Recent data associate T cells that target mutated antigens with clinical immunotherapy responses in patients with metastatic melanoma, lung cancer, or cholangiocarcinoma. Using HLA-peptide prediction algorithms, we noted that HLA-A*11:01 could potentially present mutated KRAS variants. By immunizing HLA-A*11:01 transgenic mice, we generated murine T cells and subsequently isolated T-cell receptors (TCR) highly reactive to the mutated KRAS variants G12V and G12D. Peripheral blood lymphocytes (PBL) transduced with these TCRs could recognize multiple HLA-A*11:01+ tumor lines bearing the appropriate KRAS mutations. In a xenograft model of large established tumor, adoptive transfer of these transduced PBLs reactive with an HLA-A*11:01, G12D-mutated pancreatic cell line could significantly reduce its growth in NSG mice (P = 0.002). The success of adoptive transfer of TCR-engineered T cells against melanoma and other cancers supports clinical trials with these T cells that recognize mutated KRAS in patients with a variety of common cancer types. Cancer Immunol Res; 4(3); 204–14. ©2015 AACR.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Tumors with mutant KRAS can express neoantigen fragments containing the oncogenic driver mutation on the MHC.
“Tumors with mutant KRAS can express neoantigen fragments containing the oncogenic driver mutation on the major histocompatibility complex [88,89].”
From KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance (2024) · cites this paper as [89]
The transduced peripheral blood lymphocytes recognized multiple HLA-A*11:01(+) tumor lines bearing the appropriate KRAS mutations.
“The transduced PBLs could recognize multiple HLA-A*11:01(+) tumor lines bearing the appropriate KRAS mutations.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [606]
Adoptive transfer of the transduced peripheral blood lymphocytes resulted in a significant reduction in tumor growth in a xenograft model by detecting human KRAS-mutant pancreatic cells.
“Adoptive transfer of these transduced PBLs resulted in a significant reduction in tumor growth in a xenograft model by detecting human KRAS-mutant pancreatic cells.606”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [606]
Wang and co-workers isolated highly reactive T-cell receptors to mutated KRAS variants G12V and G12D from murine T cells in immunized HLA-A*11:01 transgenic mice and transduced them into peripheral blood lymphocytes.
“In 2016, Wang and co-workers isolated highly reactive T-cell receptors (TCR) to mutated KRAS variants G12V and G12D from murine T cells in immunized HLA-A*11:01 (258) transgenic mice, which were then transduced into peripheral blood lymphocytes (PBLs).”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [606]
TCRs targeting KRASG12D and KRASG12V were produced in HLAA11:01 transgenic mice, and peripheral blood lymphocytes were generated retrovirally.
“Building on these results, TCRs targeting KRASG12D and KRASG12V were produced in HLAA11:01 transgenic mice, and peripheral blood lymphocytes were generated retrovirally [107].”
From RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches (2025) · cites this paper as [107]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989 · see citing works
Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802 · see citing works
Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma
Snyder, A., Makarov, V., Merghoub, T., Yuan, J., Zaretsky, J. M., Desrichard, A., Walsh, L. A., Postow, M. A., Wong, P., Ho, T. S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1406498 · Cited by 4,286 · see citing works
Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., et al. (2008) · Science · doi:10.1126/science.1164368 · Cited by 3,969 · see citing works
<i>K-ras</i> Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer
Karapetis, C. S., Khambata-Ford, S., Jonker, D. J., O'Callaghan, C. J., Tu, D., Tebbutt, N. C., Simes, R. J., Chalchal, H., Shapiro, J. D., Robitaille, S., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0804385 · Cited by 3,622 · see citing works
Rosenberg, S. A., Yang, J. C., Sherry, R. M., Kammula, U. S., Hughes, M. S., Phan, G. Q., Citrin, D. E., Restifo, N. P., Robbins, P. F., Wunderlich, J. R., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-0116 · Cited by 2,145 · see citing works
Self-citationCancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer
Tran, E., Turcotte, S., Gros, A., Robbins, P. F., Lu, Y., Dudley, M. E., Wunderlich, J. R., Somerville, R. P. T., Hogan, K., Hinrichs, C. S., et al. (2014) · Science · doi:10.1126/science.1251102 · Cited by 1,710 · see citing works
Self-citationKRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib
Pao, W. J., Wang, T. Y., Riely, G. J., Miller, V. A., Pan, Q., Ladanyi, M., Zakowski, M. F., Heelan, R. T., Kris, M. G., & VARMUS, H. E. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020017 · Cited by 1,517 · see citing works
Kochenderfer, J. N., Dudley, M. E., Feldman, S. A., Wilson, W. H., Spaner, D., Marić, I., Stetler‐Stevenson, M., Phan, G. Q., Hughes, M. S., Sherry, R. M., et al. (2011) · Blood · doi:10.1182/blood-2011-10-384388 · Cited by 1,441 · see citing works
Self-citationJohnson, L. A., Morgan, R. A., Dudley, M. E., Cassard, L., Yang, J. C.-H., Hughes, M. S., Kammula, U. S., Royal, R. E., Sherry, R. M., Wunderlich, J. R., et al. (2009) · Blood · doi:10.1182/blood-2009-03-211714 · Cited by 1,421 · see citing works
Self-citationParkhurst, M. R., Yang, J. C.-H., Langan, R. C., Dudley, M. E., Nathan, D.-A. N., Feldman, S. A., Davis, J. L., Morgan, R. A., Merino, M. J., Sherry, R. M., et al. (2010) · Molecular Therapy · doi:10.1038/mt.2010.272 · Cited by 1,025 · see citing works
Self-citationHeparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes
Caruana, I., Savoldo, B., Hoyos, V., Weber, G., Liu, H., Kim, E. S., Ittmann, M., Marchetti, D., & Dotti, G. (2015) · Nature Medicine · doi:10.1038/nm.3833 · Cited by 820 · see citing works
Lundegaard, C., Lamberth, K., Harndahl, M. N., Buus, S., Lund, O., & Nielsen, M. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn202 · Cited by 808 · see citing works
Robbins, P. F., Kassim, S. H., Tran, T. L. N., Crystal, J. S., Morgan, R. A., Feldman, S. A., Yang, J. C., Dudley, M. E., Wunderlich, J. R., Sherry, R. M., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-2708 · Cited by 807 · see citing works
Self-citationHruban, R. H., van Mansfeld, A. D. M., Offerhaus, G. J. A., van Weering, D. H. J., Allison, D. C., Goodman, S. N., Kensler, T. W., Bose, K., Cameron, J. L., & Bos, J. L. (1993) · PubMed Central · Cited by 650 · see citing works
Cohen, C. J., Zhao, Y., Zheng, Z., Rosenberg, S. A., & Morgan, R. A. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1450 · Cited by 465 · see citing works
Coulie, P. G., Lehmann, F. F., Lethé, B., Herman, J., Lurquin, C., Andrawiss, M., & Boon, T. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.17.7976 · Cited by 423 · see citing works
New allele frequency database: http://www.allelefrequencies.net
Middleton, D., Menchaca, L., Rood, H., & Komerofsky, R. (2003) · Tissue Antigens · doi:10.1034/j.1399-0039.2003.00062.x · Cited by 388 · see citing works
Wedén, S., Klemp, M., Gladhaug, I. P., Møller, M., Eriksen, J. A., Gaudernack, G., & Buanes, T. A. (2010) · International Journal of Cancer · doi:10.1002/ijc.25449 · Cited by 183 · see citing works
Chinnasamy, N., Wargo, J. A., Yu, Z., Rao, M., Frankel, T. L., Riley, J. P., Hong, J. J., Parkhurst, M. R., Feldman, S. A., Schrump, D. S., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001775 · Cited by 161 · see citing works
Self-citationCohen, C., Zheng, Z.-L., Bray, R., Zhao, Y.-B., Sherman, L., Rosenberg, S., & Morgan, R. (2005) · Journal of Immunology · doi:10.4049/jimmunol.175.9.5799 · Cited by 139 · see citing works
Parkhurst, M. R., Joo, J. S., Riley, J. P., Yu, Z., Li, Y., Robbins, P. F., & Rosenberg, S. A. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-1638 · Cited by 122 · see citing works
Self-citationToubaji, A., Achtar, M. S., Provenzano, M., Herrin, V. E., Behrens, R. J., Hamilton, M., Bernstein, S. A., Venzon, D. J., Gause, B. L., Marincola, F. M., et al. (2008) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-008-0477-6 · Cited by 122 · see citing works
Lang, A. H., Drexel, H., Geller-Rhomberg, S., Stark, N., Winder, T., Geiger, K. D., & Muendlein, A. (2011) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2010.11.007 · Cited by 107 · see citing works
A ras- Mutated Peptide Targeted by CTL Infiltrating a Human Melanoma Lesion
Linard, B., Bezieau, S., Benlalam, H., Labarrière, N., Guilloux, Y., Diez, E., & Jotereau, F. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.9.4802 · Cited by 88 · see citing works
STK33 kinase inhibitor BRD-8899 has no effect on KRAS-dependent cancer cell viability
Luo, T., Masson, K., Jaffe, J. D., Silkworth, W., Ross, N. T., Scherer, C., Scholl, C., Fröhling, S., Carr, S. A., Stern, A. M., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1120589109 · Cited by 86 · see citing works
Chaft, J. E., Litvak, A., Arcila, M. E., Patel, P., D'Angelo, S. P., Krug, L. M., Rusch, V., Mattson, A., Coeshott, C., Park, B., et al. (2014) · Clinical Lung Cancer · doi:10.1016/j.cllc.2014.06.002 · Cited by 78 · see citing works
Mutational analysis and clinical correlation of metastatic colorectal cancer
Russo, A. L., Borger, D. R., Szymonifka, J. D., Ryan, D. P., Wo, J. Y.-L., Blaszkowsky, L. S., Kwak, E. L., Allen, J. N., Wadlow, R. C., Zhu, A. X., et al. (2014) · Cancer · doi:10.1002/cncr.28599 · Cited by 77 · see citing works
Wang, Q. J., Hanada, K., Robbins, P. F., Li, Y. F., & Yang, J. C.-H. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-0588 · Cited by 73 · see citing works
Self-citationLaghi, L., Orbetegli, O., Bianchi, P. P., Zerbi, A., Carlo, V. D., Boland, C. R., & Malesci, A. (2002) · Oncogene · doi:10.1038/sj.onc.1205533 · Cited by 72 · see citing works
Schultz, N. A., Roslind, A., Christensen, I. J., Horn, T., Høgdall, E., Pedersen, L. N., Kruhøffer, M., Burcharth, F., Wøjdemann, M., & Johansen, J. S. (2012) · Pancreas · doi:10.1097/mpa.0b013e31823cd9df · Cited by 68 · see citing works
Rahma, O. E., Hamilton, J. M., Wojtowicz, M. E., Dakheel, O., Bernstein, S. A., Liewehr, D. J., Steinberg, S. M., & Khleif, S. N. (2014) · Journal of Translational Medicine · doi:10.1186/1479-5876-12-55 · Cited by 68 · see citing works
Naturally occurring T-cell response against mutated p21 ras oncoprotein in pancreatic cancer.
Kubuschok, B., Neumann, F., Breit, R., Sester, M., Schormann, C., Wagner, C., Sester, U., Hartmann, F., Wagner, M., REMBERGER, K., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1672 · Cited by 58 · see citing works
Gjertsen, M., Sæterdal, I., Sæbøe‐Larssen, S., & Gaudernack, G. (2003) · Journal of Molecular Medicine · doi:10.1007/s00109-002-0390-y · Cited by 29 · see citing works
Distribution of HLA-A, -B, and -C Alleles and HLA/KIR Combinations in Han Population in China
Shen, Y., Cao, D., Li, Y., Kulski, J. K., Shi, L., Jiang, H., Ma, Q., Yu, J., Zhou, J., Yao, Y., et al. (2014) · Journal of Immunology Research · doi:10.1155/2014/565296 · Cited by 21 · see citing works
Flagged first, then by citations
2 of the 37 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer
Tran, E., Robbins, P. F., Lu, Y.-C., Prickett, T. D., Gartner, J. J., Jia, L., Pasetto, A., Zheng, Z., Ray, S., Groh, E. M., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1609279 · Cited by 1,368 · see citing works
RAS-targeted therapies: is the undruggable drugged?
Moore, A. R., Rosenberg, S. C., McCormick, F., & Malek, S. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0068-6 · Cited by 1,103 · see citing works
Neoantigens: promising targets for cancer therapy
Xie, N., Shen, G., Gao, W., Huang, Z., Huang, C., & Fu, L. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01270-x · Cited by 1,020 · see citing works
Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies
Anderson, K. G., Stromnes, I. M., & Greenberg, P. D. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.02.008 · Cited by 706 · see citing works
Turning the corner on therapeutic cancer vaccines
Hollingsworth, R. E., & Jansen, K. (2019) · npj Vaccines · doi:10.1038/s41541-019-0103-y · Cited by 689 · see citing works
Challenges and Opportunities for Pancreatic Cancer Immunotherapy
Bear, A. S., Vonderheide, R. H., & O'Hara, M. H. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.08.004 · Cited by 674 · see citing works
Metabolic Regulation of T Cell Longevity and Function in Tumor Immunotherapy
Kishton, R. J., Sukumar, M., & Restifo, N. P. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.06.016 · Cited by 548 · see citing works
Self-citationRole of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer
Zhu, G., Pei, L., Xia, H., Tang, Q., & Bi, F. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01441-4 · Cited by 482 · see citing works
Emerging new therapeutic antibody derivatives for cancer treatment
Jin, S., Sun, Y., Xiao, L., Gu, X., Ning, J., Xu, Y., Chen, S., & Pan, L. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00868-x · Cited by 461 · see citing works
Identifying and Targeting Human Tumor Antigens for T Cell-Based Immunotherapy of Solid Tumors
Leko, V., & Rosenberg, S. A. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.07.013 · Cited by 449 · see citing works
Therapeutic strategies to target RAS-mutant cancers
Ryan, M. B., & Corcoran, R. B. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0105-0 · Cited by 420 · see citing works
Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works
Tumor neoantigens: from basic research to clinical applications
Jiang, T., Shi, T., Zhang, H., Hu, J., Song, Y., Wei, J., Ren, S., & Zhou, C. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0787-5 · Cited by 386 · see citing works
T cell receptor‐based cancer immunotherapy: Emerging efficacy and pathways of resistance
Chandran, S. S., & Klebanoff, C. A. (2019) · Immunological Reviews · doi:10.1111/imr.12772 · Cited by 325 · see citing works
Cancer Therapy With TCR-Engineered T Cells: Current Strategies, Challenges, and Prospects
Shafer, P. W., Somes, L. K., & Hoyos, V. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.835762 · Cited by 280 · see citing works
Challenges and new technologies in adoptive cell therapy
Zhang, P., Zhang, G., & Wan, X. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01492-8 · Cited by 271 · see citing works
Translational advances in pancreatic ductal adenocarcinoma therapy
Hosein, A. N., Dougan, S. K., Aguirre, A. J., & Maitra, A. (2022) · Nature Cancer · doi:10.1038/s43018-022-00349-2 · Cited by 249 · see citing works
Montesion, M., Murugesan, K., Jin, D. X., Sharaf, R., Sánchez, N., Guria, A., Minker, M., Li, G., Fisher, V. A., Sokol, E. S., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0672 · Cited by 244 · see citing works
Yossef, R., Tran, E., Deniger, D. C., Gros, A., Pasetto, A., Parkhurst, M. R., Gartner, J. J., Prickett, T. D., Cafri, G., Robbins, P. F., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.122467 · Cited by 209 · see citing works
Targeting public neoantigens for cancer immunotherapy
Pearlman, A. H., Hwang, M. S., Konig, M. F., Hsiue, E. H.-C., Douglass, J., DiNapoli, S. R., Mog, B. J., Bettegowda, C., Pardoll, D. M., Gabelli, S. B., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00210-y · Cited by 192 · see citing works
RAS: Striking at the Core of the Oncogenic Circuitry
Gimple, R. C., & Wang, X. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00965 · Cited by 174 · see citing works
Adoptive Cell Therapy Targeting Neoantigens: A Frontier for Cancer Research
Wang, Z., & Cao, Y. J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00176 · Cited by 181 · see citing works
Bispecific antibodies targeting mutant <i>RAS</i> neoantigens
Douglass, J., Hsiue, E. H.-C., Mog, B. J., Hwang, M. S., DiNapoli, S. R., Pearlman, A. H., Miller, M. S., Wright, K. M., Azurmendi, P. A., Wang, Q., et al. (2021) · Science Immunology · doi:10.1126/sciimmunol.abd5515 · Cited by 171 · see citing works
Self-citationExploiting the neoantigen landscape for immunotherapy of pancreatic ductal adenocarcinoma
Bailey, P. J., Chang, D. K.-F., Forget, M., Lucas, F. A. S., Alvarez, H. A., Haymaker, C., Chattopadhyay, C., Kim, S.-H., Ekmekçioglu, S., Grimm, E. A., et al. (2016) · Scientific Reports · doi:10.1038/srep35848 · Cited by 168 · see citing works
Tumor Burden and Immunotherapy: Impact on Immune Infiltration and Therapeutic Outcomes
Kim, S. I., Cassella, C. R., & Byrne, K. T. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.629722 · Cited by 169 · see citing works
Cafri, G., Yossef, R., Pasetto, A., Deniger, D. C., Lu, Y., Parkhurst, M. R., Gartner, J. J., Jia, L., Ray, S., Ngo, L. T., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08304-z · Cited by 165 · see citing works
The improbable targeted therapy: KRAS as an emerging target in non-small cell lung cancer (NSCLC)
Salgia, R., Pharaon, R. R., Mambetsariev, I., Nam, A., & Sattler, M. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100186 · Cited by 163 · see citing works
Mattos‐Arruda, L. D., Vázquez, M., Finotello, F., Lepore, R., Porta, E., Hundal, J., Amengual-Rigo, P., Ng, C. K. Y., Valencia, A., Carrillo, J., et al. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.05.008 · Cited by 159 · see citing works
Lal, N., White, B. S., Goussous, G., Pickles, O. J., Mason, M. J., Beggs, A. D., Tanière, P., Willcox, B. E., Guinney, J., & Middleton, G. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-1090 · Cited by 154 · see citing works
Exploiting the therapeutic implications of KRAS inhibition on tumor immunity
Molina-Arcas, M., & Downward, J. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.02.012 · Cited by 152 · see citing works
Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens
Wagner, S., Mullins, C. S., & Linnebacher, M. (2018) · World Journal of Gastroenterology · doi:10.3748/wjg.v24.i48.5418 · Cited by 144 · see citing works
Zhang, Z., Rohweder, P. J., Ongpipattanakul, C., Basu, K., Bohn, M.-F., Dugan, E. J., Steri, V., Hann, B., Shokat, K. M., & Craik, C. S. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.07.005 · Cited by 136 · see citing works
Pan-cancer proteogenomics expands the landscape of therapeutic targets
Savage, S. R., Yi, X., Lei, J. T., Wen, B., Zhao, H., Liao, Y., Jaehnig, E. J., Somes, L. K., Shafer, P. W., Lee, T. D., et al. (2024) · Cell · doi:10.1016/j.cell.2024.05.039 · Cited by 136 · see citing works
Recent insights into the biology of pancreatic cancer
Yao, W., Maitra, A., & Ying, H. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102655 · Cited by 125 · see citing works
Immune therapies in pancreatic ductal adenocarcinoma: Where are we now?
Hilmi, M., Bartholin, L., & Neuzillet, C. (2018) · World Journal of Gastroenterology · doi:10.3748/wjg.v24.i20.2137 · Cited by 124 · see citing works
KRAS G12D targeted therapies for pancreatic cancer: Has the fortress been conquered?
Bannoura, S. F., Khan, H. Y., & Azmi, A. S. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1013902 · Cited by 118 · see citing works
Adoptive cellular immunotherapy for solid neoplasms beyond CAR-T
Liu, Q., Li, J., Zheng, H., Yang, S., Hua, Y., Huang, N., Kleeff, J. H., Liao, Q., & Wu, W. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01735-9 · Cited by 126 · see citing works
Recent developments in immunotherapy for gastrointestinal tract cancers
Chong, X., Madeti, Y., Cai, J., Li, W., Cong, L., Lu, J., Mo, L., Liu, H., He, S., Yu, C., et al. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01578-x · Cited by 129 · see citing works
KRAS G12C in advanced NSCLC: Prevalence, co-mutations, and testing
Lim, T. K. H., Skoulidis, F., Kerr, K. M., Ahn, M., Kapp, J. R., Soares, F. A., & Yatabe, Y. (2023) · Lung Cancer · doi:10.1016/j.lungcan.2023.107293 · Cited by 126 · see citing works
Liquid Biopsy, ctDNA Diagnosis through NGS
Chen, L., Liu, X., Zheng, B., Ke, R., & Tzeng, C. (2021) · Life · doi:10.3390/life11090890 · Cited by 115 · see citing works
Bear, A. S., Blanchard, T., Cesare, J., Ford, M. J., Richman, L. P., Xu, C., Baroja, M. L., McCuaig, S., Costeas, C., Gabunia, K., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24562-2 · Cited by 113 · see citing works
Therapeutic high affinity T cell receptor targeting a KRASG12D cancer neoantigen
Poole, A. J., Karuppiah, V., Hartt, A., Haidar, J. N. S., Moureau, S., Dobrzycki, T., Hayes, C., Rowley, C. N., Dias, J. C., Harper, S. J., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32811-1 · Cited by 112 · see citing works
Neoantigen prediction and the need for validation
Vitiello, A., & Zanetti, M. (2017) · Nature Biotechnology · doi:10.1038/nbt.3932 · Cited by 108 · see citing works
Steentoft, C., Migliorini, D., King-Peoples, T. R., Mandel, U., June, C. H., & Posey, A. D. (2018) · Glycobiology · doi:10.1093/glycob/cwy008 · Cited by 101 · see citing works
KRAS G12C–Mutant Non–Small Cell Lung Cancer
Veluswamy, R., Mack, P. C., Houldsworth, J., Elkhouly, E., & Hirsch, F. R. (2021) · The Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2021.02.002 · Cited by 96 · see citing works
KRAS G12V neoantigen specific T cell receptor for adoptive T cell therapy against tumors
Lu, D., Chen, Y., Jiang, M., Wang, J., Li, Y., Ma, K., Sun, W., Zheng, X., Qi, J., Jin, W., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42010-1 · Cited by 101 · see citing works
The neoepitope landscape in pediatric cancers
Chang, T., Carter, R. A., Li, Y., Li, Y., Wang, H., Edmonson, M. N., Chen, X. '., Arnold, P. Y., Geiger, T. L., Wu, G., et al. (2017) · Genome Medicine · doi:10.1186/s13073-017-0468-3 · Cited by 97 · see citing works
Engineering Strategies to Enhance TCR-Based Adoptive T Cell Therapy
Rath, J. A., & Arber, C. (2020) · Cells · doi:10.3390/cells9061485 · Cited by 99 · see citing works
Parkhurst, M. R., Goff, S. L., Lowery, F. J., Beyer, R. K., Halas, H. K., Robbins, P. F., Prickett, T. D., Gartner, J. J., Sindiri, S., Krishna, S., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-03109-0 · Cited by 88 · see citing works
Self-citationInflammation as a driver and vulnerability of KRAS mediated oncogenesis
Kitajima, S., Thummalapalli, R., & Barbie, D. A. (2016) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2016.06.009 · Cited by 83 · see citing works
ADAM17: An Emerging Therapeutic Target for Lung Cancer
Saad, M. I., Rose‐John, S., & Jenkins, B. J. (2019) · Cancers · doi:10.3390/cancers11091218 · Cited by 80 · see citing works
Nagasaka, M., Potugari, B. R., Nguyen, A., Sukari, A. W., Azmi, A. S., & Ou, S. I. (2021) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2021.102309 · Cited by 78 · see citing works
Systematic discovery and validation of T cell targets directed against oncogenic KRAS mutations
Choi, J., Goulding, S. P., Conn, B. P., McGann, C. D., Dietze, J. L., Kohler, J., Lenkala, D., Boudot, A. J., Rothenberg, D., Turcott, P. J., et al. (2021) · Cell Reports Methods · doi:10.1016/j.crmeth.2021.100084 · Cited by 67 · see citing works
Neoantigen-targeted TCR-engineered T cell immunotherapy: current advances and challenges
Pang, Z., Lu, M., Zhang, Y., Gao, Y., Bai, J. J., Gu, J., Xie, L., & Wu, W. (2023) · Biomarker Research · doi:10.1186/s40364-023-00534-0 · Cited by 68 · see citing works
Pharmacokinetic tuning of protein–antigen fusions enhances the immunogenicity of T-cell vaccines
Mehta, N. K., Pradhan, R., Soleimany, A. P., Moynihan, K. D., Rothschilds, A. M., Momin, N., Rakhra, K., Mata-Fink, J., Bhatia, S. N., Wittrup, K. D., et al. (2020) · Nature Biomedical Engineering · doi:10.1038/s41551-020-0563-4 · Cited by 66 · see citing works
Zhang, X., Qi, Y. A., Zhang, Q., & Liu, W. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109542 · Cited by 64 · see citing works
Wang, W., Yuan, T., Ma, L., Zhu, Y., Bao, J., Zhao, X., Zhao, Y., Zong, Y., Zhang, Y., Yang, S., et al. (2022) · Advanced Science · doi:10.1002/advs.202105810 · Cited by 63 · see citing works
Shared cancer neoantigens: Making private matters public
Klebanoff, C. A., & Wolchok, J. D. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20172188 · Cited by 62 · see citing works
Abelin, J. G., Bergstrom, E. J., Rivera, K. D., Taylor, H. B., Klaeger, S., Xu, C., Verzani, E. K., White, C. J., Woldemichael, H. B., Virshup, M., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37547-0 · Cited by 61 · see citing works
Adoptive Cell Therapy for Metastatic Melanoma
Merhavi-Shoham, E., Itzhaki, O., Markel, G., Schachter, J., & Besser, M. J. (2017) · The Cancer Journal · doi:10.1097/ppo.0000000000000240 · Cited by 61 · see citing works
KRAS: Biology, Inhibition, and Mechanisms of Inhibitor Resistance
Ash, L. J., Busia-Bourdain, O., Okpattah, D., Kamel, A., Liberchuk, A., & Wolfe, A. L. (2024) · Current Oncology · doi:10.3390/curroncol31040150 · Cited by 59 · see citing works
“Clinical evaluations of KRAS inhibitors, sotorasib and adagrasib, were conducted as basket trials and included solid tumors with KRAS G12C regardless of the tissue of origin.”
BackgroundDeniger, D. C., Pasetto, A., Tran, E., Parkhurst, M. R., Cohen, C. J., Robbins, P. F., Cooper, L. J. N., & Rosenberg, S. A. (2016) · Molecular Therapy · doi:10.1038/mt.2016.51 · Cited by 59 · see citing works
Arbelaez, C. A., Estrada, J., Gessner, M. A., Glaus, C., Morales, A. B., Mohn, D., Phee, H., Lipford, J. R., & Johnston, J. A. (2020) · npj Vaccines · doi:10.1038/s41541-020-00253-9 · Cited by 56 · see citing works
Targeting the undruggable oncogenic KRAS: the dawn of hope
Asimgil, H., Ertetik, U., Çevik, N. C., Ekizce, M., Doğruöz, A., Gökalp, M., Sever, E. A., Istvánffy, R., Friess, H., Ceyhan, G. O., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.153688 · Cited by 55 · see citing works
KRAS: A Druggable Target in Colon Cancer Patients
Negri, F., Bottarelli, L., de’Angelis, G. L., & Gnetti, L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084120 · Cited by 55 · see citing works
Levin, N., Paria, B. C., Vale, N. R., Yossef, R., Lowery, F. J., Parkhurst, M. R., Yu, Z., Florentin, M., Cafri, G., Gartner, J. J., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-0849 · Cited by 54 · see citing works
Self-citationTargeting KRAS mutations: orchestrating cancer evolution and therapeutic challenges
Choucair, K., Imtiaz, H., Uddin, M. H., Nagasaka, M., Al-Hallak, M. N., Philip, P. A., El-Rayes, B., Pasche, B., & Azmi, A. S. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02473-8 · Cited by 57 · see citing works
Neoantigen-based personalized cancer vaccines: the emergence of precision cancer immunotherapy
Richard, G., Princiotta, M. F., Bridon, D. P., Martin, W. D., Steinberg, G. D., & Groot, A. S. D. (2021) · Expert Review of Vaccines · doi:10.1080/14760584.2022.2012456 · Cited by 49 · see citing works
Mishto, M., Mansurkhodzhaev, A., Ge, Y., Bitra, A., Cordfunke, R. A., Henze, S., Paul, D., Sidney, J., Urlaub, H., Neefjes, J., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02572 · Cited by 48 · see citing works
Shared Neoantigens: Ideal Targets for Off-The-Shelf Cancer Immunotherapy
Zhao, W., Wu, J., Chen, S., & Zhou, Z. M. (2020) · Pharmacogenomics · doi:10.2217/pgs-2019-0184 · Cited by 47 · see citing works
Mutated RAS: Targeting the “Untargetable” with T Cells
Chatani, P. D., & Yang, J. C. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2138 · Cited by 45 · see citing works
Self-citationIdentification of Neoantigens in Cancer Cells as Targets for Immunotherapy
Okada, M., Shimizu, K., & Fujii, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052594 · Cited by 49 · see citing works
Neoantigen cancer vaccines: a new star on the horizon
Li, X., You, J., Hong, L., Liu, W., Guo, P., & Hao, X. (2023) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2023.0395 · Cited by 52 · see citing works
Wang, X., Wang, W., Zou, S., Xu, Z., Cao, D., Zhang, S., Wei, M., Zhan, Q., Wen, C., Li, F., et al. (2024) · Cell Research · doi:10.1038/s41422-024-00990-9 · Cited by 46 · see citing works
Neoantigen-Specific Adoptive Cell Therapies for Cancer: Making T-Cell Products More Personal
Bianchi, V., Harari, A., & Coukos, G. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01215 · Cited by 47 · see citing works
Current Status of Immunotherapies for Treating Pancreatic Cancer
Wu, A. A., Jaffee, E. M., & Lee, V. (2019) · Current Oncology Reports · doi:10.1007/s11912-019-0811-5 · Cited by 45 · see citing works
Neoantigens in Hematologic Malignancies
Biernacki, M. A., & Bleakley, M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00121 · Cited by 46 · see citing works
Targeting neoantigens for cancer immunotherapy: Table 1.
Lu, Y., & Robbins, P. F. (2016) · International Immunology · doi:10.1093/intimm/dxw026 · Cited by 44 · see citing works
Bräunlein, E., & Krackhardt, A. M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01702 · Cited by 42 · see citing works
T-Cell Transfer Therapy Targeting Mutant KRAS
Maoz, A., Rennert, G., & Gruber, S. B. (2017) · New England Journal of Medicine · doi:10.1056/nejmc1616637 · Cited by 43 · see citing works
Parikh, A. Y., Masi, R., Gasmi, B., Hanada, K., Parkhurst, M. R., Gartner, J. J., Sindiri, S., Prickett, T. D., Robbins, P. F., Zacharakis, N., et al. (2023) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-023-03476-6 · Cited by 41 · see citing works
Self-citationMutant RAS and the tumor microenvironment as dual therapeutic targets for advanced colorectal cancer
Janssen, J. B. E., Medema, J. P., Gootjes, E. C., Tauriello, D. V. F., & Verheul, H. M. W. (2022) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2022.102433 · Cited by 41 · see citing works
John, S., Antonia, S. J., Rose, T. A., Seifert, R. P., Centeno, B. A., Wagner, A. S., & Creelan, B. (2017) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-017-0258-x · Cited by 39 · see citing works
Structural engineering of chimeric antigen receptors targeting HLA-restricted neoantigens
Hwang, M. S., Miller, M. S., Thirawatananond, P., Douglass, J., Wright, K. M., Hsiue, E. H.-C., Mog, B. J., Aytenfisu, T. Y., Murphy, M. B., Azurmendi, P. A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25605-4 · Cited by 38 · see citing works
Advancements and Challenges in Peptide-Based Cancer Vaccination: A Multidisciplinary Perspective
Liu, D., Liu, L., Li, X., Wang, S., Wu, G., & Che, X. (2024) · Vaccines · doi:10.3390/vaccines12080950 · Cited by 38 · see citing works
Discovery through clinical sequencing in oncology
Donoghue, M. T. A., Schram, A. M., Hyman, D. M., & Taylor, B. S. (2020) · Nature Cancer · doi:10.1038/s43018-020-0100-0 · Cited by 38 · see citing works
Cinausero, M., Laprovitera, N., Maglio, G. D., Gerratana, L., Riefolo, M., Macerelli, M., Fiorentino, M., Porcellini, E., Buoro, V., Gelsomino, F., et al. (2019) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758835919885540 · Cited by 36 · see citing works
Targeting RAS mutants in malignancies: successes, failures, and reasons for hope
Yang, H. S., Zhou, X., Fu, D., Le, C., Wang, J., Zhou, Q., Liu, X., Yuan, Y., Ding, K., & Xiao, Q. (2022) · 癌症：英文版 · doi:10.1002/cac2.12377 · Cited by 35 · see citing works
Targeting tumor tolerance: A new hope for pancreatic cancer therapy?
Delitto, D., Wallet, S. M., & Hughes, S. J. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.06.008 · Cited by 36 · see citing works
Update on Targeted Therapy in Medullary Thyroid Cancer
Okafor, C. I., Hogan, J., Raygada, M. J., Thomas, B. J., Akshintala, S., Glod, J. W., & Rivero, J. D. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.708949 · Cited by 36 · see citing works
Wei, T., Leisegang, M., Xia, M., Kiyotani, K., Li, F., Zeng, C., Deng, C., Jiang, J., Harada, M., Agrawal, N., et al. (2021) · OncoImmunology · doi:10.1080/2162402x.2021.1929726 · Cited by 33 · see citing works
Mutant KRAS Peptide Targeted CAR-T Cells Engineered for Cancer Therapy
Benton, A., Liu, J.-G., Poussin, M., Goldgewicht, A. L., Udawela, M., Bear, A. S., Wellhausen, N., Carreno, B. M., Smith, P., Beasley, M. D., et al. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.05.006 · Cited by 32 · see citing works
Zhou, J., Zhao, W., Wu, J., Lu, J., Ding, Y., Wu, S., Wang, H., Ding, D., Mo, F., Zhou, Z. M., et al. (2019) · BioMed Research International · doi:10.1155/2019/8103142 · Cited by 32 · see citing works
Moradi, A., Pourseif, M. M., Jafari, B., Parvizpour, S., & Omidi, Y. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104790 · Cited by 31 · see citing works
Emerging Therapies in the Management of Advanced-Stage Gastric Cancer
Kumar, V., Soni, P., Garg, M., Kamholz, S. L., & Chandra, A. B. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00404 · Cited by 31 · see citing works
Hinrichs, C. S. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1294 · Cited by 30 · see citing works
Targeting KRAS in Non-Small Cell Lung Cancer
de la Fuente, E. C., Olmedo, M. E., Rueda, A. G., Lage, Y., & Garrido, P. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2021.792635 · Cited by 33 · see citing works
Immune vulnerabilities of mutant KRAS in pancreatic cancer
Cheng, N. C., & Vonderheide, R. H. (2023) · Trends in cancer · doi:10.1016/j.trecan.2023.07.004 · Cited by 30 · see citing works
Empirical and Rational Design of T Cell Receptor-Based Immunotherapies
Jones, H. F., Molvi, Z., Klatt, M. G., Dao, T., & Scheinberg, D. A. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.585385 · Cited by 28 · see citing works
Lee, M. S., & Pant, S. (2021) · American Society of Clinical Oncology Educational Book · doi:10.1200/edbk_321255 · Cited by 29 · see citing works
- Authors
- Wang, Q. J., Yu, Z., Griffith, K., Hanada, K.-I., Restifo, N. P., & Yang, J. C.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Wang, Qiong J.
- Yang, James C.
- Venue
- Cancer Immunology Research
- Published
- 2016-02-29
- Volume
- 4
- Issue
- 3
- Pages
- 204-214
- ISSN
- 2326-6066 (ISSN-L)
- 2326-6074
- PMC
- PMC4775432
- OpenAlex
- W2239878160
- Cited by
- 240
- References
- 37
- Citations by year
- 2026: 17 · 2025: 27 · 2024: 27 · 2023: 30 · 2022: 36 · 2021: 29 · 2020: 24 · 2019: 19 · 2018: 11 · 2017: 13 · 2016: 7
- FWCI
- 10.11
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cancer Immunology Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 CA999999)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- KRAS mutation, T cell receptor engineering, neoantigens, HLA-A*11:01, pancreatic cancer, adoptive T cell therapy, xenograft tumor growth, cancer immunotherapy
- MeSH terms
- Amino Acid Sequence, Animals, Humans, Lymph Nodes, Mice, Transgenic, Neoplasm Transplantation, Pancreatic Neoplasms, Receptors, Antigen, T-Cell, Spleen, Proto-Oncogene Proteins p21(ras), Mice, SCID, Mice, Inbred NOD, Adoptive Transfer, Mutation, Missense, Cell Line, Tumor, HLA-A11 Antigen
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
