TGF‐β–responsive CAR‐T cells promote anti‐tumor immune function
Open accessAbstract
A chimeric antigen receptor (CAR) that responds to transforming growth factor beta (TGF-β) enables the engineering of T cells that convert this immunosuppressive cytokine into a potent T-cell stimulant. However, clinical translation of TGF-β CAR-T cells for cancer therapy requires the ability to productively combine TGF-β responsiveness with tumor-targeting specificity. Furthermore, the potential concern that contaminating, TGF-β?producing regulatory T (Treg) cells may preferentially expand during TGF-β CAR-T cell manufacturing and suppress effector T (Teff) cells demands careful evaluation. Here, we demonstrate that TGF-β CAR-T cells significantly improve the anti-tumor efficacy of neighboring cytotoxic T cells. Furthermore, the introduction of TGF-β CARs into mixed T-cell populations does not result in the preferential expansion of Treg cells, nor do TGF-β CAR-Treg cells cause CAR-mediated suppression of Teff cells. These results support the utility of incorporating TGF-β CARs in the development of adoptive T-cell therapy for cancer.
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?
High TGF-β signaling has been implicated in resistance to various anti-cancer treatments including chemotherapies and molecularly-targeted therapies.
“High TGF-β signaling has been implicated in resistance to various anti-cancer treatments including chemotherapies and molecularly-targeted therapies149,380,381.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [380]
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
Molecular Mechanisms of Stress-Responsive Changes in Collagen and Elastin Networks in Skin
Aziz, J., Shezali, H., Radzi, Z., Yahya, N. A., Abu Kassim, N. H., Czernuszka, J., & Rahman, M. T. (2016) · Skin Pharmacology and Physiology · doi:10.1159/000447017 · Cited by 7,323 · see citing works
Vignali, D. A. A., Collison, L. W., & Workman, C. J. (2008) · Nature Reviews Immunology · doi:10.1038/nri2343 · Cited by 3,463 · see citing works
Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma
Zaretsky, J. M., Garcia-Diaz, A., Shin, D. S., Escuin-Ordinas, H., Hugo, W., Hu-Lieskovan, S., Torrejon, D. Y., Abril-Rodriguez, G., Sandoval, S., Barthly, L., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1604958 · Cited by 3,237 · see citing works
Macrophage Cytokines: Involvement in Immunity and Infectious Diseases
Arango Duque, G., & Descoteaux, A. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00491 · Cited by 2,708 · see citing works
CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells
Liu, W., Putnam, A. L., Xu-yu, Z., Szot, G. L., Lee, M. R., Zhu, S., Gottlieb, P. A., Kapranov, P., Gingeras, T. R., de St. Groth, B. F., et al. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20060772 · Cited by 2,606 · see citing works
CD19 CAR–T cells of defined CD4+:CD8+ composition in adult B cell ALL patients
Turtle, C. J., Hanafi, L.-A., Berger, C., Gooley, T. A., Cherian, S., Hudecek, M., Sommermeyer, D., Melville, K., Pender, B., Budiarto, T. M., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85309 · Cited by 2,112 · see citing works
Yu, Q., & Stamenkovic, I. (2000) · PubMed · Cited by 1,952 · see citing works
Yu, Q., & Stamenkovic, I. (2000) · Genes & Development · doi:10.1101/gad.14.2.163 · Cited by 1,754 · see citing works
Immunosuppressive Strategies that are Mediated by Tumor Cells
Rabinovich, G. A., Gabrilovich, D. I., & Sotomayor, E. M. (2006) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141609 · Cited by 1,699 · see citing works
Robbins, P. F., Morgan, R. A., Feldman, S. A., Yang, J. C.-H., Sherry, R. M., Dudley, M. E., Wunderlich, J. R., Nahvi, A. V., Helman, L. J., Mackall, C. L., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.32.2537 · Cited by 1,635 · see citing works
Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer
Siegel, P. M., & Massagué, J. (2003) · Nature reviews. Cancer · doi:10.1038/nrc1208 · Cited by 1,600 · see citing works
Nakamura, K., Kitani, A., & Strober, W. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.5.629 · Cited by 1,596 · see citing works
The roles of TGFβ in the tumour microenvironment
Pickup, M. W., Novitskiy, S. V., & Moses, H. L. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3603 · Cited by 915 · see citing works
Sommermeyer, D., Hudecek, M., Kosasih, P. L., Gogishvili, T., Maloney, D. G., Turtle, C. J., & Riddell, S. R. (2015) · Leukemia · doi:10.1038/leu.2015.247 · Cited by 864 · see citing works
Regulatory T cells: how do they suppress immune responses?
Sakaguchi, S., Wing, K., Onishi, Y., Martín, P. P., & Yamaguchi, T. (2009) · International Immunology · doi:10.1093/intimm/dxp095 · Cited by 850 · see citing works
Chen, M.-L., Pittet, M. J., Gorelik, L., Flavell, R. A., Weissleder, R., von Boehmer, H., & Khazaie, K. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408197102 · Cited by 806 · see citing works
Roles of TGF-beta in hepatic fibrosis
Gressner, A. M. (2002) · Frontiers in bioscience · doi:10.2741/a812 · Cited by 785 · see citing works
T-helper-1-cell cytokines drive cancer into senescence
Braumüller, H., Wieder, T., Brenner, E., Aßmann, S., Hahn, M., Alkhaled, M., Schilbach, K., Essmann, F., Kneilling, M., Griessinger, C., et al. (2013) · Nature · doi:10.1038/nature11824 · Cited by 720 · see citing works
Increase of regulatory T cells in the peripheral blood of cancer patients.
Wolf, A. M., Wolf, D. G. F., Steurer, M., Gastl, G., Gunsilius, E., & Grubeck-Loebenstein, B. (2003) · PubMed · Cited by 655 · see citing works
Targeting the TGFβ pathway for cancer therapy
Neuzillet, C., Tijeras‐Raballand, A., Cohen, R., Cros, J. F., Faivre, S. J., Raymond, É., & Gramont, A. D. E. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.11.001 · Cited by 610 · see citing works
Zah, E., Lin, M.-Y., Silva-Benedict, A., Jensen, M. C., & Chen, Y. Y. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0231 · Cited by 609 · see citing works
Self-citationWang, X., Chang, W.-C., Wong, C. W., Colcher, D. M., Sherman, M. A., Ostberg, J. R., Forman, S. J., Riddell, S. R., & Jensen, M. C. (2011) · Blood · doi:10.1182/blood-2011-02-337360 · Cited by 600 · see citing works
Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor
MacDonald, K. G., Hoeppli, R. E., Huang, Q. B., Gillies, J. K., Luciani, D. S., Orban, P. C., Broady, R. C., & Levings, M. K. (2016) · Journal of Clinical Investigation · doi:10.1172/jci82771 · Cited by 488 · see citing works
Liu, V. C., Wong, L. Y., Jang, T. L., Shah, A. H., Park, I. I., Yang, X. J., Zhang, Q., Lonning, S. M., Teicher, B. A., & Lee, C. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.5.2883 · Cited by 453 · see citing works
Hinrichs, C., Borman, Z. A., Cassard, L., Gattinoni, L., Spolski, R., Yu, Z.-Y., Sanchez-Perez, L., Muranski, P., Kern, S., Logun, C., et al. (2009) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0907448106 · Cited by 407 · see citing works
CAR/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery
Fransson, M., Piras, E., Burman, J., Nilsson, B., Essand, M., Lu, B., Harris, R. A., Magnusson, P. U., Brittebo, E., & Loskog, A. S. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-112 · Cited by 372 · see citing works
Bollard, C. M., Rössig, C., Calonge, M. J., Huls, M. H., Wagner, H.-J., Massagué, J., Brenner, M. K., Heslop, H. E., & Rooney, C. M. (2002) · Blood · doi:10.1182/blood.v99.9.3179 · Cited by 316 · see citing works
Determinants of Successful CD8+ T-Cell Adoptive Immunotherapy for Large Established Tumors in Mice
Klebanoff, C. A., Gattinoni, L., Palmer, D. C., Muranski, P. J., Ji, Y., Hinrichs, C. S., Borman, Z. A., Kerkar, S. P., Scott, C. D., Finkelstein, S. E., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-0503 · Cited by 288 · see citing works
Rewiring T-cell responses to soluble factors with chimeric antigen receptors
Chang, Z. L., Lorenzini, M. H., Chen, X., Tran, U., Bangayan, N. J., & Chen, Y. Y. (2018) · Nature Chemical Biology · doi:10.1038/nchembio.2565 · Cited by 259 · see citing works
Self-citationBlat, D., Zigmond, E., Alteber, Z., Waks, T., & Eshhar, Z. (2014) · Molecular Therapy · doi:10.1038/mt.2014.41 · Cited by 246 · see citing works
Antitumor Activity of EBV-specific T Lymphocytes Transduced With a Dominant Negative TGF-β Receptor
Foster, A. E., Dotti, G., Lu, A., Khalil, M., Brenner, M. K., Heslop, H. E., Rooney, C. M., & Bollard, C. M. (2008) · Journal of Immunotherapy · doi:10.1097/cji.0b013e318177092b · Cited by 210 · see citing works
In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell proliferation
Earle, K., Tang, Q., Zhou, X., Liu, W., Zhu, S., Bonyhadi, M. L., & Bluestone, J. A. (2005) · Clinical Immunology · doi:10.1016/j.clim.2005.02.017 · Cited by 183 · see citing works
Bollard, C. M., Tripic, T., Cruz, C. R., Dotti, G., Gottschalk, S., Torrano, V., Dakhova, O., Carrum, G., Ramos, C. A., Liu, H., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.74.3179 · Cited by 181 · see citing works
Lin, J. T., Martin, S. L., Xia, L., & Gorham, J. D. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.174.10.5950 · Cited by 163 · see citing works
Yoon, J., Schmidt, A., Zhang, A.-H., Königs, C., Kim, Y. C., & Scott, D. W. (2017) · Blood · doi:10.1182/blood-2016-07-727834 · Cited by 150 · see citing works
Zhang, Q., Yang, X. J., Pins, M., Javonovic, B., Kuzel, T. M., Kim, S., Parijs, L. V., Greenberg, N. M., Liu, V., Guo, Y., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3169 · Cited by 146 · see citing works
CARs: Synthetic Immunoreceptors for Cancer Therapy and Beyond
Chang, Z., & Chen, Y. Y. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.03.002 · Cited by 104 · see citing works
Self-citationImmunotherapy of autoimmune encephalomyelitis with redirected CD4+CD25+ T lymphocytes
Mekala, D. J., & Geiger, T. L. (2004) · Blood · doi:10.1182/blood-2004-09-3579 · Cited by 103 · see citing works
Zhang, L., Yu, Z., Muranski, P. J., Palmer, D. C., Restifo, N. P., Rosenberg, S. A., & Morgan, R. (2012) · Gene Therapy · doi:10.1038/gt.2012.75 · Cited by 93 · see citing works
Naturally Arising CD25+CD4+ Regulatory T Cells in Tumor Immunity
Nomura, T., & Sakaguchi, S. (2005) · Springer eBooks · doi:10.1007/3-540-27702-1_13 · Cited by 92 · see citing works
Khan, S. A., Joyce, J., & Tsuda, T. (2012) · BMC Research Notes · doi:10.1186/1756-0500-5-636 · Cited by 87 · see citing works
Jin, P., Zhao, Y., Liu, H., Chen, J., Ren, J., Jin, J., Bedognetti, D., Liu, S., Wang, E., Marincola, F. M., et al. (2016) · Scientific Reports · doi:10.1038/srep26345 · Cited by 84 · see citing works
Junker, U., Knöfel, B., Nuske, K., Rebstock, K., Steiner, T., Wunderlich, H., Junker, K., & Reinhold, D. (1996) · Cytokine · doi:10.1006/cyto.1996.0105 · Cited by 77 · see citing works
Hombach, A. A., Kofler, D. M., Rappl, G., & Abken, H. (2009) · Gene Therapy · doi:10.1038/gt.2009.75 · Cited by 69 · see citing works
Tokuno, K., Hazama, S., Yoshino, S., Yoshida, S., & Oka, M. (2009) · PubMed · Cited by 44 · see citing works
Wang, L., Wen, W., Yuan, J., Helfand, B. T., Yu, L., Shi, C., Tian, F., Zheng, J., Wang, F., Chen, L. V., et al. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1758 · Cited by 43 · see citing works
Nguyen, P., Moisini, I., & Geiger, T. L. (2003) · Blood · doi:10.1182/blood-2003-04-1255 · Cited by 36 · see citing works
Quatromoni, J. G., Wang, Y., Vo, D. D., Morris, L. F., Jazirehi, A. R., McBride, W. H., Chatila, T. A., Koya, R. C., & Economou, J. S. (2012) · Journal of Translational Medicine · doi:10.1186/1479-5876-10-127 · Cited by 31 · see citing works
Flagged first, then by citations
1 of the 49 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Lung cancer immunotherapy: progress, pitfalls, and promises
Lahiri, A., Maji, A., Potdar, P. D., Singh, N., Parikh, P., Bisht, B., Mukherjee, A., & Paul, M. K. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01740-y · Cited by 1,102 · see citing works
TGFβ biology in cancer progression and immunotherapy
Derynck, R., Turley, S. J., & Akhurst, R. J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0403-1 · Cited by 944 · see citing works
Engineering CAR-T Cells for Next-Generation Cancer Therapy
Hong, M., Clubb, J. D., & Chen, Y. Y. (2020) · Cancer Cell · doi:10.1016/j.ccell.2020.07.005 · Cited by 644 · see citing works
Self-citationMakni‐Maalej, K., Merhi, M., Inchakalody, V. P., Mestiri, S., Alam, M. A., Maccalli, C., Cherif, H., Shahab Uddin, M. S., Steinhoff, M. S., Marincola, F. M., et al. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01723-z · Cited by 638 · see citing works
Navigating CAR-T cells through the solid-tumour microenvironment
Hou, A. J., Chen, L. C., & Chen, Y. Y. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00189-2 · Cited by 556 · see citing works
Self-citationImproving CAR-T immunotherapy: Overcoming the challenges of T cell exhaustion
Gumber, D., & Wang, L. D. (2022) · EBioMedicine · doi:10.1016/j.ebiom.2022.103941 · Cited by 409 · see citing works
Overcoming TGFβ-mediated immune evasion in cancer
Tauriello, D. V. F., Sancho, E., & Batlle, E. (2022) · Nature Reviews Cancer · doi:10.1038/s41568-021-00413-6 · Cited by 377 · see citing works
The Natural Cytotoxicity Receptors in Health and Disease
Barrow, A. D., Martin, C. J., & Colonna, M. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00909 · Cited by 370 · see citing works
FoxP3+ T regulatory cells in cancer: Prognostic biomarkers and therapeutic targets
Saleh, R., & Elkord, E. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.07.022 · Cited by 355 · see citing works
CAR T cell therapy and the tumor microenvironment: Current challenges and opportunities
Fonkoua, L. A. K., Sirpilla, O. L., Sakemura, R. L., Siegler, E. L., & Kenderian, S. S. (2022) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2022.03.009 · Cited by 299 · see citing works
Chlorotoxin-directed CAR T cells for specific and effective targeting of glioblastoma
Wang, D., Starr, R., Chang, W.-C., Aguilar, B., Alizadeh, D., Wright, S. L., Yang, X., Brito, A., Sarkissian, A., Ostberg, J. R., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aaw2672 · Cited by 215 · see citing works
CAR T cells for brain tumors: Lessons learned and road ahead
Akhavan, D., Alizadeh, D., Wang, D., Weist, M. R., Shepphird, J. K., & Brown, C. E. (2019) · Immunological Reviews · doi:10.1111/imr.12773 · Cited by 211 · see citing works
Sorkhabi, A. D., Khosroshahi, L. M., Sarkesh, A., Mardi, A., Aghebati‐Maleki, A., Maleki, L. A., & Baradaran, B. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1113882 · Cited by 215 · see citing works
Immunosuppression in tumor immune microenvironment and its optimization from CAR-T cell therapy
Liu, Z., Zhou, Z., Dang, Q., Xu, H. M., Lv, J., Li, H., & Han, X. (2022) · Theranostics · doi:10.7150/thno.76854 · Cited by 198 · see citing works
Adoptive cell therapy for cancer treatment
Du, S., Yan, J., Xue, Y., Zhong, Y., & Dong, Y. (2023) · Exploration · doi:10.1002/exp.20210058 · Cited by 114 · see citing works
Current state and next-generation CAR-T cells in multiple myeloma
Manier, S., Ingegnere, T., Escure, G., Prodhomme, C., Nudel, M., Mitra, S., & Facon, T. T. F. (2022) · Blood Reviews · doi:10.1016/j.blre.2022.100929 · Cited by 112 · see citing works
Chuntova, P., Chow, F. E., Watchmaker, P. B., Galvez, M., Heimberger, A. B., Newell, E. W., Diaz, A. A., DePinho, R. A., Li, M. O., Wherry, E. J., et al. (2020) · Neuro-Oncology · doi:10.1093/neuonc/noaa277 · Cited by 89 · see citing works
Self-citationThe Role of TGF-β in Bone Metastases
Trivedi, T., Pagnotti, G. M., Guise, T. A., & Mohammad, K. S. (2021) · Biomolecules · doi:10.3390/biom11111643 · Cited by 91 · see citing works
Target selection of CAR T cell therapy in accordance with the TME for solid tumors.
Liu, B., Yan, L., & Zhou, M. (2019) · Europe PMC (PubMed Central) · Cited by 78 · see citing works
Li, N., Rodriguez, J. L., Yin, Y., Logun, M. T., Zhang, L., Yu, S., Hicks, K., Zhang, J. V., Zhang, L., Xie, C., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.07.020 · Cited by 74 · see citing works
Khan, S. H., Choi, Y., Veena, M. S., Lee, J. K., & Shin, D. S. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1489827 · Cited by 79 · see citing works
Advances in CAR-T Cell Genetic Engineering Strategies to Overcome Hurdles in Solid Tumors Treatment
Andrea, A. E., Chiron, A., Mallah, S., Bessoles, S., Sarrabayrouse, G., & Hacein‐Bey‐Abina, S. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.830292 · Cited by 75 · see citing works
Hou, A. J., Shih, R. M., Uy, B. R., Shafer, A. M., Chang, Z. L., Comin-Anduix, B., Güemes, M., Galić, Z., Phyu, S. M., Okada, H., et al. (2024) · Neuro-Oncology · doi:10.1093/neuonc/noae126 · Cited by 77 · see citing works
Self-citationJung, I.-Y., Noguera-Ortega, E., Bartoszek, R. L., Collins, S. M., Williams, E. F., Suhoski, M. M., Jadlowsky, J. K., Plesa, G., Siegel, D. L., Chew, A., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101053 · Cited by 72 · see citing works
TGF-β and Cancer Immunotherapy
Maruyama, T., Chen, W., & Shibata, H. (2022) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b21-00966 · Cited by 68 · see citing works
Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models
Si, X., Xiao, L., Brown, C. E., & Wang, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063154 · Cited by 69 · see citing works
Engineering chimeric antigen receptor T cells for solid tumour therapy
Liu, L., Qu, Y., Cheng, L., Yoon, C. W., He, P., Monther, A., Guo, T., Chittle, S. J., & Wang, Y. (2022) · Clinical and Translational Medicine · doi:10.1002/ctm2.1141 · Cited by 59 · see citing works
Zhou, Z., Wang, J., Wang, J., Yang, S., Wang, R., Zhang, G., Li, Z., Shi, R., Wang, Z., & Lu, Q. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02047-2 · Cited by 62 · see citing works
Molecular Engineering of the TGF-β Signaling Pathway
Zi, Z. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.05.022 · Cited by 54 · see citing works
Alishah, K., Birtel, M., Masoumi, E., Jafarzadeh, L., Mirzaei, H. R., Hadjati, J., Voss, R.-H., Diken, M., & Asad, S. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-03146-0 · Cited by 50 · see citing works
Recent updates on chimeric antigen receptor T cell therapy for hepatocellular carcinoma
Guo, J., & Tang, Q. (2021) · Cancer Gene Therapy · doi:10.1038/s41417-020-00259-4 · Cited by 48 · see citing works
CAR T cells: engineered immune cells to treat brain cancers and beyond
Huang, Z., Dewanjee, S., Chakraborty, P., Jha, N. K., Dey, A., Gangopadhyay, M., Chen, X.-Y., Wang, J., & Jha, S. K. (2023) · Molecular Cancer · doi:10.1186/s12943-022-01712-8 · Cited by 45 · see citing works
Engineering Next-Generation CAR-T Cells: Overcoming Tumor Hypoxia and Metabolism
Gao, T. A., & Chen, Y. Y. (2022) · Annual Review of Chemical and Biomolecular Engineering · doi:10.1146/annurev-chembioeng-092120-092914 · Cited by 41 · see citing works
Self-citationChallenges and strategies associated with CAR-T cell therapy in blood malignancies
Liu, Z., Lei, W., Wang, H., Liu, X., & Fu, R. (2024) · Experimental Hematology and Oncology · doi:10.1186/s40164-024-00490-x · Cited by 43 · see citing works
A Roadmap of CAR-T-Cell Therapy in Glioblastoma: Challenges and Future Perspectives
Montoya, M., Gallus, M., Phyu, S. M., Haegelin, J., de Groot, J., & Okada, H. (2024) · Cells · doi:10.3390/cells13090726 · Cited by 40 · see citing works
CAR‐T‐cell products in solid tumors: Progress, challenges, and strategies
Qian, K., Li, G., Zhang, S., Fu, W., Li, T., Zhao, J., Lei, C., Wang, Y., & Hu, S. (2024) · Interdisciplinary medicine · doi:10.1002/inmd.20230047 · Cited by 34 · see citing works
Radiotherapy as a means to increase the efficacy of T-cell therapy in solid tumors
Laurent, P.-A., Morel, D., Meziani, L., Depil, S., & Deutsch, É. (2022) · OncoImmunology · doi:10.1080/2162402x.2022.2158013 · Cited by 34 · see citing works
New advances in cancer therapy targeting TGF-β signaling pathways
Shou, M., Zhou, H., & Ma, L. (2023) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2023.100755 · Cited by 32 · see citing works
CAR T Cell Therapy Progress and Challenges for Solid Tumors
Stern, L. A., Jönsson, V. D., & Priceman, S. J. (2020) · Cancer treatment and research · doi:10.1007/978-3-030-38862-1_11 · Cited by 32 · see citing works
Therapeutic Implications of TGFβ in Cancer Treatment: A Systematic Review
Gómez‐Gil, V. (2021) · Cancers · doi:10.3390/cancers13030379 · Cited by 32 · see citing works
Rana, P. S., Soler, D. C., Kort, J., & Driscoll, J. J. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1059715 · Cited by 34 · see citing works
Hartley, J., & Abken, H. (2019) · Clinical & Translational Immunology · doi:10.1002/cti2.1064 · Cited by 30 · see citing works
Cancer-Homing CAR-T Cells and Endogenous Immune Population Dynamics
Guerra, E., Pietro, R. D., Basile, M., Trerotola, M., & Alberti, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms23010405 · Cited by 30 · see citing works
Naeem, M., Hazafa, A., Bano, N., Ali, R., Farooq, M., Razak, S. I. A., Lee, T. Y., & Devaraj, S. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121409 · Cited by 31 · see citing works
Exploring the potential of TGFβ as a diagnostic marker and therapeutic target against cancer
Garg, P. K., Pareek, S., Kulkarni, P., Horne, D., Salgia, R., & Singhal, S. S. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116646 · Cited by 31 · see citing works
Coengineering specificity, safety, and function into T cells for cancer immunotherapy
Attianese, G. M. P. G., Ash, S., & Irving, M. B. (2023) · Immunological Reviews · doi:10.1111/imr.13252 · Cited by 29 · see citing works
CAR-engineered cell therapies: current understandings and future perspectives
Bayat, M., & Nahand, J. S. (2026) · Molecular Biomedicine · doi:10.1186/s43556-025-00401-4 · Cited by 31 · see citing works
TGFβ: Signaling Blockade for Cancer Immunotherapy
Chen, S., Mamaï, O., & Akhurst, R. J. (2021) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-070620-103554 · Cited by 28 · see citing works
Functional Diversities of Regulatory T Cells in the Context of Cancer Immunotherapy
Gao, R., Shi, G., & Wang, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.833667 · Cited by 28 · see citing works
Abken, H. (2021) · Human Gene Therapy · doi:10.1089/hum.2021.165 · Cited by 26 · see citing works
Engineering primary T cells with chimeric antigen receptors for rewired responses to soluble ligands
Chang, Z., Hou, A. J., & Chen, Y. Y. (2020) · Nature Protocols · doi:10.1038/s41596-020-0294-8 · Cited by 25 · see citing works
Self-citationNovel Cellular Therapies for Hepatocellular Carcinoma
Roddy, H., Meyer, T., & Roddie, C. (2022) · Cancers · doi:10.3390/cancers14030504 · Cited by 25 · see citing works
Innovative strategies to advance CAR T cell therapy for solid tumors.
Huang, M., Jinniu, D., Gao, L., & Zhou, J. (2020) · PubMed Central · Cited by 24 · see citing works
Advances and Hurdles in CAR T Cell Immune Therapy for Solid Tumors
Boccalatte, F. E., Mina, R., Aroldi, A., Leone, S., Suryadevara, C. M., Placantonakis, D. G., & Bruno, B. (2022) · Cancers · doi:10.3390/cancers14205108 · Cited by 23 · see citing works
Acute Myeloid Leukemia: Is It T Time?
Khoud, M. B., Ingegnere, T., Quesnel, B., Mitra, S., & Brinster, C. (2021) · Cancers · doi:10.3390/cancers13102385 · Cited by 22 · see citing works
Gökçe, K., Aykor, A., Ersoy, M., Özel, E., & Soyman, M. (2008) · PubMed · Cited by 19 · see citing works
How Can We Engineer CAR T Cells to Overcome Resistance?
Glover, M., Avraamides, S., & Maher, J. F. (2021) · Biologics · doi:10.2147/btt.s252568 · Cited by 19 · see citing works
Spiga, M., Martini, E., Maffia, M. C., Ciceri, F., Ruggiero, E., Potenza, A., & Bonini, C. (2024) · Seminars in Immunopathology · doi:10.1007/s00281-024-01011-y · Cited by 15 · see citing works
Probiotic-guided CAR-T cells for universal solid tumor targetingPreprint
Vincent, R. L., Gurbatri, C. R., Redenti, A., Coker, C., Arpaia, N., & Danino, T. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.10.463366 · Cited by 13 · see citing works
CAR-T cell therapy: Advances in digestive system malignant tumors
Xu, N., Wu, Z., Pan, J., Xu, X. L., & Wei, Q. (2024) · Molecular Therapy Oncology · doi:10.1016/j.omton.2024.200872 · Cited by 12 · see citing works
Swanson, E. R., Köse, E., Zollinger, E. A., & Elliott, S. (2022) · Bulletin of Mathematical Biology · doi:10.1007/s11538-022-01015-5 · Cited by 11 · see citing works
West, A. G., Digby, A., Santure, A. W., Guhlin, J. G., Dearden, P. K., Kākāpō Recovery Team, Taylor, M. W., & Urban, L. (2023) · Molecular Ecology · doi:10.1111/mec.16999 · Cited by 11 · see citing works
CAR-T cell technologies that interact with the tumour microenvironment in solid tumours
Taylor, C. A., Glover, M., & Maher, J. F. (2024) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2024.2380894 · Cited by 12 · see citing works
Niu, X., Zhang, P., Dai, L., Peng, X., Liu, Z., Tang, Y., Zhang, G., & Wan, X. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-010237 · Cited by 11 · see citing works
Zalka, C. V. (2012) · Digital Commons - East Tennessee State University (East Tennessee State University) · Cited by 11 · see citing works
Advancing Immunotherapy in Pancreatic Cancer: A Brief Review of Emerging Adoptive Cell Therapies
Sherpally, D., & Manne, A. (2025) · Cancers · doi:10.3390/cancers17040589 · Cited by 13 · see citing works
Engineering Principles for Synthetic Biology Circuits in Cancer Immunotherapy
Shih, R. M., & Chen, Y. Y. (2022) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-21-0769 · Cited by 10 · see citing works
Self-citationTransforming growth factor-β micro-environment mediated immune cell functions in cervical cancer
Gnanagurusamy, J., Krishnamoorthy, S., & Muthusami, S. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112837 · Cited by 9 · see citing works
Synthesizing a Smarter CAR T Cell: Advanced Engineering of T-cell Immunotherapies
Zhu, I., Piraner, D. I., & Roybal, K. T. (2023) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-22-0962 · Cited by 9 · see citing works
CAR‐T Therapy in Clinical Practice: Technical Advances and Current Challenges
Ren, P., Zhang, C., Li, W., Wang, X., Liang, A., Yang, G., Xu, H., & Ma, P. (2022) · Advanced Biology · doi:10.1002/adbi.202101262 · Cited by 9 · see citing works
The soldiers needed to be awakened: Tumor-infiltrating immune cells
Yaping, W., Wang, Z., Zhuling, C., Li, R., Pengyu, F., Lili, G., Cheng, J., Bo, Z., Liu, L., Guangdong, H., et al. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.988703 · Cited by 9 · see citing works
Bar, O., Porgador, A., & Cooks, T. (2024) · Journal of Extracellular Biology · doi:10.1002/jex2.70011 · Cited by 8 · see citing works
Sharma, M., Shetty, S. S., Soi, S., & Radhakrishnan, R. A. (2024) · Journal of Oral Biology and Craniofacial Research · doi:10.1016/j.jobcr.2024.10.008 · Cited by 8 · see citing works
de Folmont, A. D. T., Bourhis, J.-H., Chouaı̈b, S., & Terry, S. (2021) · Immuno · doi:10.3390/immuno1030010 · Cited by 8 · see citing works
Barzegari, A., Salemi, F., Kamyab, A., Aratikatla, A., Nejati, N., Valizade, M., Eltouny, E., & Ebrahimi, A. (2024) · Journal of bone oncology · doi:10.1016/j.jbo.2024.100635 · Cited by 8 · see citing works
Outsmarting and outmuscling cancer cells with synthetic and systems immunology
Chen, L. C., & Chen, Y. Y. (2019) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2019.01.016 · Cited by 8 · see citing works
Self-citationRen, T., & Huang, Y. B. (2024) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-024-03443-7 · Cited by 8 · see citing works
Overcoming resistance to anti‐CD19 CAR T‐cell therapy in B‐cell malignancies
Yang, X., Wei, J., & Zhou, J. (2022) · Hematological Oncology · doi:10.1002/hon.3036 · Cited by 7 · see citing works
The development of CAR T cells for patients with CNS malignancies
Binder, Z. A., Bagley, S. J., Foster, J., & O’Rourke, D. M. (2025) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-025-01102-1 · Cited by 5 · see citing works
Photonanozyme–Kras–ribosome combination treatment of non-small cell lung cancer after COVID-19
Si, Q., Bai, M., Wang, X., Wang, T., & Qin, Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1420463 · Cited by 5 · see citing works
Targeting the immune-privileged myofibroblast in oral submucous fibrosis by CAR T-cell therapy
Sarode, S. C., Sharma, N. K., Sarode, G. S., Sharma, M., & Radhakrishnan, R. A. (2022) · Medical Hypotheses · doi:10.1016/j.mehy.2022.110897 · Cited by 5 · see citing works
Toward the clinical development of synthetic immunity to cancer
Garcia, J. M., Burnett, C. E., & Roybal, K. T. (2023) · Immunological Reviews · doi:10.1111/imr.13245 · Cited by 7 · see citing works
Novel approaches to promote CAR T-cell function in solid tumors
Hull, C., & Maher, J. F. (2019) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2019.1614164 · Cited by 5 · see citing works
Research progress on resistance mechanisms to CAR-T cell therapy in diffuse large B-cell lymphoma
Zhang, S., Liu, J., & Li, Z. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1696105 · Cited by 5 · see citing works
Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy
Chen, Z., & Zhou, X. (2025) · Acta Biochimica et Biophysica Sinica · doi:10.3724/abbs.2025190 · Cited by 4 · see citing works
Cheng, Z., Cui, X., Li, S., Liang, Y., Yang, W., Ouyang, J., Wei, M., Yan, Z., & Yu, W. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117229 · Cited by 4 · see citing works
ARIAWAN, T. R., Divasta, I. G. M., BINTARI, A., de Liyis, B. G., & Wihandani, D. M. (2025) · Journal of Oncological Sciences · doi:10.37047/jos.galenos.2024.2024.104258 · Cited by 3 · see citing works
Cytokines and immune effector cell therapy
Haugh, A. M., & Frigault, M. J. (2025) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2025.101628 · Cited by 3 · see citing works
Alabi, F. A., Okpalanwaka, I. F., Oyegbesan, A., Okoyeocha, E. O. M., Oladejo, M., & Imodoye, S. O. (2025) · MedComm – Oncology · doi:10.1002/mog2.70027 · Cited by 3 · see citing works
Cytokine-driven cancer immune evasion mechanisms
Arenas, E. J. (2025) · International review of cytology · doi:10.1016/bs.ircmb.2025.01.004 · Cited by 5 · see citing works
Therapeutic applications of engineered chimeric antigen receptors-T cell for cancer therapy
Hussain, A. (2022) · Beni-Suef University Journal of Basic and Applied Sciences · doi:10.1186/s43088-022-00238-8 · Cited by 3 · see citing works
Next-generation immunotherapy biologics for glioblastoma
Schonfeld, E., Sjoholm, A., Ha, J. P. Y., Liu, J., Nageeb, G., Annagiri, S., Kim, L. H., Choi, J. H., & Lim, M. K. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1775093 · Cited by 2 · see citing works
Wang, D., Starr, R., Chang, W.-C., Aguilar, B., Alizadeh, D., Wright, S. L., Yang, X., Brito, A., Sarkissian, A., Ostberg, J. R., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.01.24.918888 · Cited by 2 · see citing works
Kayser, V., & Şen, M. (2020) · doi:10.1002/9781119564690.ch13 · Cited by 2 · see citing works
CIMT 2021: report on the 18th Annual Meeting of the Association for Cancer Immunotherapy
Billmeier, A., Khinvasara, K., Lang, F., Mohr, J., Reidenbach, D., Schork, M., Yildiz, I., & Diken, M. (2022) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2021.2024416 · Cited by 1 · see citing works
CAR-T-Cell Therapy for Solid Tumors
Duggirala, S. (2025) · Springer eBooks · doi:10.1007/978-3-031-88695-9_6 · Cited by 1 · see citing works
Franklin, J., Pophali, P. A., Jackson, Z., Wald, D. N., & Avigan, D. (2024) · Wiley eBooks · doi:10.1002/9781394180486.ch25 · Cited by 1 · see citing works
Programming Novel Cancer Therapeutics: Design Principles for Chimeric Antigen Receptors
Hou, A. J., & Chen, Y. Y. (2021) · Wiley eBooks · doi:10.1002/9783527815128.ch14
Self-citationLuan, R., & Deng, B. (2023) · Hematology and Oncology Discovery · doi:10.15212/hod-2022-0009
- Authors
- Hou, A. J., Chang, Z. L., Lorenzini, M. H., Zah, E., & Chen, Y. Y.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Chen, Yvonne Y.
- Venue
- Bioengineering & Translational Medicine
- Publisher
- Wiley
- Published
- 2018-05
- Volume
- 3
- Issue
- 2
- Pages
- 75-86
- ISSN
- 2380-6761 (ISSN-L)
- PMC
- PMC6063867
- OpenAlex
- W2807108630
- Cited by
- 106
- References
- 49
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 19 · 2023: 15 · 2022: 22 · 2021: 14 · 2020: 10 · 2019: 8 · 2012: 1
- FWCI
- 3.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Bioengineering & Translational Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (DP5OD012133, F30CA183528, T32 GM067555)
- National Cancer Institute
- National Center for Advancing Translational Sciences
- National Institute of General Medical Sciences
- National Heart, Lung, and Blood Institute
- NIH Office of the Director
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- chimeric antigen receptor, adoptive T cell therapy, antitumor immunity, regulatory T cells, effector T cells, TGF-beta signaling, immunosuppression, cancer immunotherapy
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