Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, in Advanced Solid Tumors
Open accessPublished version of a preprint
Abstract
Purpose: M7824 (MSB0011359C) is an innovative first-in-class bifunctional fusion protein composed of a mAb against programmed death ligand 1 (PD-L1) fused to a TGFβ “trap.” Experimental Design: In the 3+3 dose-escalation component of this phase I study (NCT02517398), eligible patients with advanced solid tumors received M7824 at 1, 3, 10, or 20 mg/kg once every 2 weeks until confirmed progression, unacceptable toxicity, or trial withdrawal; in addition, a cohort received an initial 0.3 mg/kg dose to evaluate pharmacokinetics/pharmacodynamics, followed by 10 mg/kg dosing. The primary objective is to determine the safety and maximum tolerated dose (MTD); secondary objectives include pharmacokinetics, immunogenicity, and best overall response. Results: Nineteen heavily pretreated patients with ECOG 0–1 have received M7824. Grade ≥3 treatment-related adverse events occurred in four patients (skin infection secondary to localized bullous pemphigoid, asymptomatic lipase increase, colitis with associated anemia, and gastroparesis with hypokalemia). The MTD was not reached. M7824 saturated peripheral PD-L1 and sequestered any released plasma TGFβ1, -β2, and -β3 throughout the dosing period at >1 mg/kg. There were signs of efficacy across all dose levels, including one ongoing confirmed complete response (cervical cancer), two durable confirmed partial responses (PR; pancreatic cancer; anal cancer), one near-PR (cervical cancer), and two cases of prolonged stable disease in patients with growing disease at study entry (pancreatic cancer; carcinoid). Conclusions: M7824 has a manageable safety profile in patients with heavily pretreated advanced solid tumors. Early signs of efficacy are encouraging, and multiple expansion cohorts are ongoing in a range of tumors. Clin Cancer Res; 24(6); 1287–95. ©2018 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?
Initial dose escalation studies of galunisertib or other TβRI kinase inhibitors mandated monitoring for cardiotoxicity due to heart valve dysplasia that was observed in rats and dogs receiving high doses of drug.
“Initial dose escalation studies of galunisertib or other TβRI kinase inhibitors mandated monitoring for cardiotoxicity due to heart valve dysplasia that was observed in rats and dogs receiving high doses of drug340,341.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [340]
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
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,314 · see citing works
Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1507643 · Cited by 9,335 · see citing works
Herbst, R. S., Baas, P., Kim, D.-W., Felip, E., Pérez-Gracia, J. L., Han, J.-Y., Molina, J., Kim, J.-H., Arvis, C. D., Ahn, M.-J., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01281-7 · Cited by 6,449 · see citing works
Pembrolizumab versus Ipilimumab in Advanced Melanoma
Robert, C., Schachter, J., Long, G. V., Arance, A., Grob, J. J., Mortier, L., Daud, A., Carlino, M. S., McNeil, C., Lotem, M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1503093 · Cited by 5,887 · see citing works
Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma
Motzer, R. J., Escudier, B., McDermott, D. F., George, S., Hammers, H. J., Srinivas, S., Tykodi, S. S., Sosman, J. A., Procopio, G., Plimack, E. R., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1510665 · Cited by 5,807 · see citing works
Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck
Ferris, R. L., Blumenschein, G., Fayette, J., Guigay, J., Colevas, A. D., Licitra, L., Harrington, K., Kasper, S., Vokes, E. E., Even, C., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1602252 · Cited by 5,101 · see citing works
Nivolumab and ipilimumab versus ipilimumab in untreated melanoma
Postow, M. A., Chesney, J., Pavlick, A. C., Robert, C., Grossmann, K., McDermott, D., Linette, G. P., Meyer, N., Giguere, J. K., Agarwala, S. S., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1414428 · Cited by 2,781 · see citing works
Fehrenbacher, L., Spira, A., Ballinger, M., Kowanetz, M., Vansteenkiste, J., Mazieres, J., Park, K., Smith, D., Artal-Cortes, A., Lewanski, C., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00587-0 · Cited by 2,756 · see citing works
Weber, J. S., D’Angelo, S. P., Minor, D. R., Hodi, F. S., Gutzmer, R., Neyns, B., Höeller, C., Khushalani, N. I., Miller, W. H., Lao, C. D., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)70076-8 · Cited by 2,676 · see citing works
Seiwert, T. Y., Burtness, B., Mehra, R., Weiss, J., Berger, R., Eder, J. P., Heath, K., McClanahan, T., Lunceford, J., Gause, C., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30066-3 · Cited by 1,745 · cited 2× · see citing works
“Aside from the keratoacanthomas, the safety profile of M7824 was similar to that of anti–PD-1/PD-L1 agents (1-13), including anticipated treatment-related AEs that were immune related (eg, bullous pemphigoid and colitis) and manageable with a course of corticosteroids.”
BackgroundResultKaufman, H. L., Russell, J., Hamid, O., Bhatia, S., Terheyden, P., D'Angelo, S. P., Shih, K. C., Lebbé, C., Linette, G. P., Milella, M., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30364-3 · Cited by 1,236 · see citing works
Self-citationTargeting TGF-β Signaling in Cancer
Colak, S., & ten Dijke, P. (2017) · Trends in cancer · doi:10.1016/j.trecan.2016.11.008 · Cited by 1,003 · see citing works
Chow, L. Q. M., Haddad, R. I., Gupta, S., Mahipal, A., Mehra, R., Tahara, M., Berger, R., Eder, J. P., Burtness, B. A., Lee, S., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.68.1478 · Cited by 859 · see citing works
Massard, C., Gordon, M. S., Sharma, S., Rafii, S., Wainberg, Z. A., Luke, J., Curiel, T. J., Colon-Otero, G., Hamid, O., Sanborn, R. E., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.67.9761 · Cited by 840 · see citing works
Evolving synergistic combinations of targeted immunotherapies to combat cancer
Melero, I., Berman, D. M., Aznar, M. A., Korman, A. J., Perez‐Gracia, J. L., & Haanen, J. B. A. G. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3973 · Cited by 633 · see citing works
Apolo, A. B., Infante, J. R., Balmanoukian, A., Patel, M. R., Wang, D., Kelly, K., Mega, A. E., Britten, C. D., Ravaud, A., Mita, A. C., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.71.6795 · Cited by 585 · see citing works
Self-citationBruna, A., Darken, R. S., Rojo, F., Ocaña, A., Peñuelas, S., Arias, A., Parı́s, R., Tortosa, A., Mora, J., Baselga, J. M., et al. (2007) · Cancer Cell · doi:10.1016/j.ccr.2006.11.023 · Cited by 472 · see citing works
Dual targeting strategies with bispecific antibodies
Kontermann, R. E. (2012) · mAbs · doi:10.4161/mabs.4.2.19000 · Cited by 438 · see citing works
PD-L1 and Survival in Solid Tumors: A Meta-Analysis
Wu, P., Wu, D., Li, L., Chai, Y., & Huang, J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131403 · Cited by 351 · see citing works
Heery, C. R., Coyne, G. O., Madan, R. A., Cordes, L. M., Rajan, A., Rauckhorst, M., Lamping, E., Oyelakin, I., Marté, J. L., Lepone, L. M., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30239-5 · Cited by 308 · see citing works
Self-citationDavid, J. M., Dominguez, C., McCampbell, K. K., Gulley, J. L., Schlom, J., & Palena, C. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1349589 · Cited by 180 · see citing works
Self-citationTransforming Growth Factor-β and the Immune Response to Malignant Disease
Teicher, B. A. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-1654 · Cited by 159 · see citing works
Lacouture, M. E., Morris, J. C., Lawrence, D. P., Tan, A. R., Olencki, T. E., Shapiro, G. I., Dezube, B. J., Berzofsky, J. A., Hsu, F. J., & Guitart, J. (2015) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-015-1653-0 · Cited by 145 · see citing works
Tolcher, A. W., Berlin, J. D., Cosaert, J., Kauh, J., Chan, E., Piha-Paul, S. A., Amaya, A., Tang, S., Driscoll, K., Kimbung, R., et al. (2017) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-017-3245-5 · Cited by 105 · see citing works
Donahue, R. N., Lepone, L. M., Grenga, I., Jochéms, C., Fantini, M. C., Madan, R. A., Heery, C. R., Gulley, J. L., & Schlom, J. (2017) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-017-0220-y · Cited by 92 · see citing works
Self-citationPD-L1 over-expression and survival in patients with non-small cell lung cancer: a meta-analysis.
Zhou, Z., Zhan, P., & Song, Y. (2015) · PubMed · doi:10.3978/j.issn.2218-6751.2015.03.02 · Cited by 73 · see citing works
Zhou, F., Jiang, T., Ma, W., Gao, G., Chen, X., & Zhou, C. (2015) · Lung Cancer · doi:10.1016/j.lungcan.2015.06.005 · Cited by 65 · see citing works
Prognostic Role of PD-L1 in Malignant Solid Tumors: A Meta-Analysis
Pyo, J., Kang, G., & Kim, J. Y. (2017) · The International Journal of Biological Markers · doi:10.5301/jbm.5000225 · Cited by 60 · see citing works
Lepone, L. M., Donahue, R. N., Grenga, I., Metenou, S., Richards, J., Heery, C. R., Madan, R. A., Gulley, J. L., & Schlom, J. (2016) · Journal of Circulating Biomarkers · doi:10.5772/62322 · Cited by 57 · see citing works
Self-citationTgf-β1 expression as a biomarker of poor prognosis in prostate cancer
Reis, S. T., Pontes-Júnior, J., Antunes, A. A., de Sousa-Canavez, J. M., Abe, D. K., da Cruz, J. A. S., Dall’Oglio, M. F., Crippa, A., PASSEROTTI, C. C., Ribeiro‐Filho, L. A., et al. (2011) · Clinics · doi:10.1590/s1807-59322011000700004 · Cited by 52 · see citing works
Considerations for the combination of anticancer vaccines and immune checkpoint inhibitors
Strauss, J., Madan, R. A., & Gulley, J. L. (2016) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2016.1170805 · Cited by 31 · see citing works
Self-citationPrognostic value of programed death ligand 1 in patients with solid tumors: A meta-analysis
Jin, Y., Zhao, J., Shi, X., & Yu, X. (2015) · Journal of Cancer Research and Therapeutics · doi:10.4103/0973-1482.163837 · Cited by 13 · see citing works
Clinical Implications of TβRII Expression in Breast Cancer
Gao, N., Zhai, Q., Li, Y., Huang, K., Bian, D., Wang, X., Liu, C., Xu, H., & Zhang, T. (2015) · PLoS ONE · doi:10.1371/journal.pone.0141412 · Cited by 8 · see citing works
Flagged first, then by citations
1 of the 35 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Cancer immunoediting and resistance to T cell-based immunotherapy
O’Donnell, J. S., Teng, M. W. L., & Smyth, M. J. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0142-8 · Cited by 1,759 · see citing works
Regulatory T cells in cancer immunosuppression — implications for anticancer therapy
Togashi, Y., Shitara, K., & Nishikawa, H. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0175-7 · Cited by 1,553 · see citing works
Combination strategies with PD-1/PD-L1 blockade: current advances and future directions
Yi, M., Zheng, X., Niu, M., Zhu, S., Ge, H., & Wu, K. (2022) · Molecular Cancer · doi:10.1186/s12943-021-01489-2 · Cited by 1,445 · see citing works
TGF-β signaling in health, disease and therapeutics
Deng, Z., Fan, T. T., Chu, X., Tian, H., Zheng, Y., Li, C., & He, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01764-w · Cited by 1,270 · see citing works
Targeting TGF-β signal transduction for fibrosis and cancer therapy
Peng, D., Fu, M., Wang, M., Wei, Y., & Wei, X. (2022) · Molecular Cancer · doi:10.1186/s12943-022-01569-x · Cited by 1,106 · 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
Next generation of immune checkpoint therapy in cancer: new developments and challenges
Marin-Acevedo, J. A., Dholaria, B., Soyano, A. E., Knutson, K. L., Chumsri, S., & Lou, Y. (2018) · Journal of Hematology & Oncology · doi:10.1186/s13045-018-0582-8 · Cited by 802 · see citing works
Combination strategies to maximize the benefits of cancer immunotherapy
Zhu, S., Zhang, T., Zheng, L., Liu, H., Song, W., Liu, D., Li, Z., & Pan, C.-X. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01164-5 · Cited by 654 · see citing works
Cancer-associated fibroblasts: from basic science to anticancer therapy
Yang, D., Liu, J., Qian, H., & Zhuang, Q. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01013-0 · Cited by 572 · see citing works
Targeting cytokine and chemokine signaling pathways for cancer therapy
Yi, M., Li, T., Niu, M., Zhang, H., Wu, Y., Wu, K., & Dai, Z. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01868-3 · Cited by 491 · see citing works
Novel therapies emerging in oncology to target the TGF‐β pathway
Kim, B.-G., Malek, E., Choi, S. H., Ignatz-Hoover, J. J., & Driscoll, J. J. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01053-x · Cited by 453 · see citing works
Genomic correlates of response to immune checkpoint blockade
Keenan, T. E., Burke, K. P., & Van Allen, E. M. (2019) · Nature Medicine · doi:10.1038/s41591-019-0382-x · Cited by 448 · see citing works
Targeting TGFβ signal transduction for cancer therapy
Liu, S., Ren, J., & ten Dijke, P. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00436-9 · Cited by 413 · see citing works
Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches
Tufail, M., Jiang, C., & Li, N. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02280-1 · Cited by 424 · 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
Tumor Immune Microenvironment during Epithelial–Mesenchymal Transition
Taki, M., Abiko, K., Ukita, M., Murakami, R., Yamanoi, K., Yamaguchi, K. D., Hamanishi, J., Baba, T., Matsumura, N., & Mandai, M. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-4459 · Cited by 357 · see citing works
Molecular therapies for HCC: Looking outside the box
Faivre, S. J., Rimassa, L., & Finn, R. S. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2019.09.010 · Cited by 327 · see citing works
Communication between EMT and PD-L1 signaling: New insights into tumor immune evasion
Jiang, Y., & Zhan, H. (2020) · Cancer Letters · doi:10.1016/j.canlet.2019.10.013 · Cited by 319 · see citing works
Biomarker-guided therapy for colorectal cancer: strength in complexity
Sveen, A., Kopetz, S., & Lothe, R. A. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0241-1 · Cited by 320 · see citing works
Molecular classification and therapeutic targets in extrahepatic cholangiocarcinoma
Montal, R., Sia, D., Montironi, C., Leow, W. Q., Esteban-Fabró, R., Pinyol, R., Torres‐Martín, M., Bassaganyas, L., Moeini, A., Peix, J., et al. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.03.008 · Cited by 304 · see citing works
Immuno-Oncology: Emerging Targets and Combination Therapies
Marshall, H. T., & Djamgoz, M. B. A. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00315 · Cited by 299 · see citing works
TGF ‐β as a driver of fibrosis: physiological roles and therapeutic opportunities
Budi, E. H., Schaub, J. R., Decaris, M. L., Turner, S., & Derynck, R. (2021) · The Journal of Pathology · doi:10.1002/path.5680 · Cited by 300 · see citing works
Cancer‐associated fibroblasts in breast cancer: Challenges and opportunities
Hu, D., Li, Z., Zheng, B., Lin, X., Pan, Y., Gong, P., Zhuo, W., Hu, Y., Chen, C., Chen, L., et al. (2022) · 癌症：英文版 · doi:10.1002/cac2.12291 · Cited by 293 · see citing works
Lee, J., Shklovskaya, E., Lim, S. Y., Carlino, M. S., Menzies, A. M., Stewart, A., Pedersen, B., Irvine, M., Alavi, S., Yang, J. Y. H., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15726-7 · Cited by 288 · see citing works
Signaling pathways in cancer‐associated fibroblasts: recent advances and future perspectives
Fang, Z., Meng, Q., Xu, J., Wang, W., Zhang, B., Liu, J., Liang, C., Hua, J., Zhao, Y., Yu, X., et al. (2022) · 癌症：英文版 · doi:10.1002/cac2.12392 · Cited by 292 · see citing works
Clinical development of therapies targeting TGFβ: current knowledge and future perspectives
Ciardiello, D., Élez, E., Tabernero, J. M., & Seoane, J. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2020.07.009 · Cited by 271 · see citing works
Lind, H., Gameiro, S. R., Jochems, C., Donahue, R. N., Strauss, J., Gulley, J. L., Palena, C., & Schlom, J. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2019-000433 · Cited by 247 · see citing works
Self-citationChristenson, E. S., Jaffee, E. M., & Azad, N. S. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30795-8 · Cited by 242 · see citing works
The efficacy of PD-1/PD-L1 blockade in cold cancers and future perspectives
Majidpoor, J., & Mortezaee, K. (2021) · Clinical Immunology · doi:10.1016/j.clim.2021.108707 · Cited by 236 · see citing works
Yi, M., Zhang, J., Li, A., Niu, M., Yan, Y., Jiao, Y., Luo, S., Zhou, P., & Wu, K. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01045-x · Cited by 233 · see citing works
Exploiting innate immunity for cancer immunotherapy
Yi, M., Li, T., Niu, M., Mei, Q., Zhao, B., Chu, Q., Dai, Z., & Wu, K. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01885-w · Cited by 236 · see citing works
Immune checkpoint inhibitors: The linchpins of modern immunotherapy
Wilky, B. A. (2019) · Immunological Reviews · doi:10.1111/imr.12766 · Cited by 210 · see citing works
If we build it they will come: targeting the immune response to breast cancer
Gatti-Mays, M. E., Balko, J. M., Gameiro, S. R., Bear, H. D., Prabhakaran, S., Fukui, J. A., Disis, M. L., Nanda, R., Gulley, J. L., Kalinsky, K. M., et al. (2019) · npj Breast Cancer · doi:10.1038/s41523-019-0133-7 · Cited by 207 · see citing works
Self-citationPaz-Ares, L. G., Kim, T. M., Vicente, D., Felip, E., Lee, D. H., Lee, K. H., Lin, C., Flor, M. J., Nicola, M. D., Alvarez, R. M., et al. (2020) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2020.03.003 · Cited by 205 · see citing works
Self-citationOverview of current targeted therapy in gallbladder cancer
Song, X., Hu, Y., Li, Y., Shao, R., Liu, F., & Liu, Y. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00324-2 · Cited by 202 · see citing works
Knudson, K. M., Hicks, K. C., Luo, X., Chen, J.-Q., Schlom, J., & Gameiro, S. R. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1426519 · Cited by 195 · see citing works
Self-citationIpilimumab and Gemcitabine for Advanced Pancreatic Cancer: A Phase Ib Study
Kamath, S. D., Kalyan, A., Kircher, S. M., Nimeiri, H. S., Fought, A. J., Benson, A. B., & Mulcahy, M. F. (2019) · The Oncologist · doi:10.1634/theoncologist.2019-0473 · Cited by 196 · see citing works
Trial watch: IDO inhibitors in cancer therapy
Naour, J. L., Galluzzi, L., Zitvogel, L., Kroemer, G., & Vacchelli, E. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1777625 · Cited by 188 · see citing works
David, J. M., Dominguez, C., McCampbell, K. K., Gulley, J. L., Schlom, J., & Palena, C. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1349589 · Cited by 180 · see citing works
Self-citationImmunogenicity of immunomodulatory, antibody-based, oncology therapeutics
Davda, J. P., Declerck, P. J., Hu‐Lieskovan, S., Hickling, T. P., Jacobs, I. A., Chou, J., Salek‐Ardakani, S., & Kraynov, E. A. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0586-0 · Cited by 181 · see citing works
Dual inhibition of TGF‐β and PD‐L1: a novel approach to cancer treatment
Gulley, J. L., Schlom, J., Barcellos‐Hoff, M. H., Wang, X., Seoane, J., Audhuy, F., Lan, Y., Dussault, I., & Moustakas, A. (2021) · Molecular Oncology · doi:10.1002/1878-0261.13146 · Cited by 178 · see citing works
Self-citationRadiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect
Nishiga, Y., Drainas, A. P., Baron, M., Bhattacharya, D., Barkal, A. A., Ahrari, Y., Mancusi, R. A., Ross, J., Takahashi, N., Thomas, A., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00456-0 · Cited by 177 · see citing works
Yi, M., Niu, M., Wu, Y., Ge, H., Jiao, D., Zhu, S., Zhang, J., Yan, Y., Zhou, P., Chu, Q., et al. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01363-8 · Cited by 176 · see citing works
Strauss, J., Gatti-Mays, M. E., Cho, B. C., Hill, A., Salas, S., McClay, E. F., Redman, J. M., Sater, H. A., Donahue, R. N., Jochéms, C., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001395 · Cited by 153 · see citing works
Self-citationYoo, C., Oh, D. Y., Choi, H. J., Kudo, M., Ueno, M., Kondo, S., Chen, L.-T., Osada, M., Helwig, C., Dussault, I., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000564 · Cited by 151 · see citing works
Self-citationImpairment of NKG2D-Mediated Tumor Immunity by TGF-β
Lazarova, M., & Steinle, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.02689 · Cited by 149 · see citing works
Transforming Growth Factor-β: A Multifunctional Regulator of Cancer Immunity
Xue, V. W., Chung, J. Y., Córdoba, C. A. G., Cheung, A. H. K., Kang, W., Lam, E. W. ‐., Leung, K. T., To, K., Lan, H. Y., & Tang, P. M. (2020) · Cancers · doi:10.3390/cancers12113099 · Cited by 149 · see citing works
Stüber, T. N., Monjezi, R., Wallstabe, L., Kühnemundt, J., Nietzer, S., Dandekar, G., Wöckel, A., Einsele, H., Wischhusen, J., & Hudecek, M. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000676 · Cited by 146 · see citing works
Tumor Plasticity and Resistance to Immunotherapy
Horn, L. A., Fousek, K., & Palena, C. (2020) · Trends in cancer · doi:10.1016/j.trecan.2020.02.001 · Cited by 142 · see citing works
Tertiary lymphoid structures and B lymphocytes in cancer prognosis and response to immunotherapies
Jacquelot, N., Tellier, J., Nutt, S. L., & Belz, G. T. (2021) · OncoImmunology · doi:10.1080/2162402x.2021.1900508 · Cited by 142 · see citing works
Regulatory T Cells in Tumor Microenvironment and Approach for Anticancer Immunotherapy
Kim, J.-H., Kim, B. S., & Lee, S. (2020) · Immune Network · doi:10.4110/in.2020.20.e4 · Cited by 143 · see citing works
TGFβ control of immune responses in cancer: a holistic immuno-oncology perspective
Nixon, B. G., Gao, S., Wang, X., & Li, M. O. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00796-z · Cited by 138 · see citing works
Unleashing Natural Killer Cells in the Tumor Microenvironment–The Next Generation of Immunotherapy?
Ben‐Shmuel, A., Biber, G., & Barda‐Saad, M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00275 · Cited by 134 · see citing works
Cytokine and Chemokine Signals of T‐Cell Exclusion in Tumors
Zhang, Y., Guan, X.-Y., & Jiang, P. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.594609 · Cited by 133 · see citing works
Recent Findings in the Regulation of Programmed Death Ligand 1 Expression
Shen, X., Zhang, L., Li, J., Li, Y., Wang, Y., & Xu, Z. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01337 · Cited by 131 · see citing works
Immune Checkpoint Inhibitors in the Treatment of HCC
Donisi, C., Puzzoni, M., Ziranu, P., Lai, E., Mariani, S., Saba, G., Impera, V., Dubois, M., Persano, M., Migliari, M., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2020.601240 · Cited by 130 · see citing works
Horn, L. A., Chariou, P. L., Gameiro, S. R., Qin, H., Iida, M., Fousek, K., Meyer, T. J., Cam, M. C., Flies, D. B., Langermann, S., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci155148 · Cited by 128 · see citing works
Self-citationChallenges for immunotherapy for the treatment of platinum resistant ovarian cancer
Saux, O. L., Ray-Coquard, I. L., & Labidi‐Galy, S. I. (2020) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.08.017 · Cited by 125 · see citing works
Cancer-Associated Fibroblasts: Versatile Players in the Tumor Microenvironment
Ganguly, D., Chandra, R., Karalis, J. D., Teke, M. E., Aguilera, T. A., Maddipati, R., Wachsmann, M., Ghersi, D., Siravegna, G., Zeh, H. J., et al. (2020) · Cancers · doi:10.3390/cancers12092652 · Cited by 122 · see citing works
Zhao, F., Evans, K., Xiao, C., DeVito, N., Theivanthiran, B., Holtzhausen, A., Siska, P. J., Blobe, G. C., & Hanks, B. A. (2018) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-18-0086 · Cited by 117 · see citing works
Principe, D. R., Narbutis, M., Kumar, S., Park, A. J., Viswakarma, N., Dorman, M. J., Kamath, S. D., Grippo, P. J., Fishel, M. L., Hwang, R. F., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-19-2959 · Cited by 123 · see citing works
Li, Z., Song, W., Rubinstein, M. P., & Liu, D. (2018) · Journal of Hematology & Oncology · doi:10.1186/s13045-018-0684-3 · Cited by 118 · see citing works
Recruitment and Expansion of Tregs Cells in the Tumor Environment—How to Target Them?
Cinier, J., Hubert, M., Besson, L., Roio, A. D., Rodriguez, C., Lombardi, V., Caux, C., & Ménétrier‐Caux, C. (2021) · Cancers · doi:10.3390/cancers13081850 · Cited by 119 · see citing works
Roles of TGF-β signaling pathway in tumor microenvirionment and cancer therapy
Zhao, H., Wei, J., & Sun, J. M. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.107101 · Cited by 117 · see citing works
Expanding the Boundaries of Biotherapeutics with Bispecific Antibodies
Husain, B., & Ellerman, D. A. (2018) · BioDrugs · doi:10.1007/s40259-018-0299-9 · Cited by 116 · see citing works
Roles of the RANKL–RANK axis in antitumour immunity — implications for therapy
Ahern, E. S., Smyth, M. J., Dougall, W. C., & Teng, M. W. L. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0095-y · Cited by 114 · see citing works
Tumor metastasis: Mechanistic insights and therapeutic interventions
Liu, M., Yang, J., Xu, B.-S., & Zhang, X. (2021) · MedComm · doi:10.1002/mco2.100 · Cited by 112 · see citing works
Radioimmunotherapy for the treatment of head and neck cancer.
Karam, S., & Raben, D. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30306-7 · Cited by 81 · see citing works
Recent developments with immunotherapy for hepatocellular carcinoma
Waidmann, O. (2018) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2018.1499722 · Cited by 103 · see citing works
Zhang, J., Hu, Z., Horta, C. A., & Yang, J. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.12.002 · Cited by 103 · see citing works
Combination therapy for pancreatic cancer: anti-PD-(L)1-based strategy
Liu, L., Huang, X., Shi, F., Song, J., Guo, C., Yang, J., Liang, T., & Bai, X. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02273-w · Cited by 103 · see citing works
Biology drives the discovery of bispecific antibodies as innovative therapeutics
Nie, S., Wang, Z., Moscoso‐Castro, M., D'Souza, P., Lei, C., Xu, J., & Gu, J. (2020) · Antibody Therapeutics · doi:10.1093/abt/tbaa003 · Cited by 95 · see citing works
TGF-β: A novel predictor and target for anti-PD-1/PD-L1 therapy
Yi, M., Li, T., Niu, M., Wu, Y., Zhao, Z., & Wu, K. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1061394 · Cited by 94 · see citing works
Colton, M., Cheadle, E. J., Honeychurch, J., & Illidge, T. (2020) · Radiation Oncology · doi:10.1186/s13014-020-01678-1 · Cited by 95 · see citing works
Interplay between coagulation and inflammation in cancer: Limitations and therapeutic opportunities
Bauer, A. T., Gorzelanny, C., Gebhardt, C., Pantel, K., & Schneider, S. W. (2021) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2021.102322 · Cited by 93 · see citing works
Cho, B. C., Daste, A., Ravaud, A., Salas, S., Isambert, N., McClay, E. F., Awada, A. H., Borel, C., Ojalvo, L. S., Helwig, C., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000664 · Cited by 92 · see citing works
Self-citationTGFβ-Directed Therapeutics: 2020
Teicher, B. A. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107666 · Cited by 92 · see citing works
Transforming growth factor β signaling pathway: A promising therapeutic target for cancer
Chen, Y., Di, C., Zhang, X., Wang, J., Wang, F., Yan, J., Xu, C., Zhang, J., Zhang, Q., Li, H., et al. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.29108 · Cited by 87 · see citing works
Cai, W., Dong, Z.-N., Fu, X.-T., Lin, L., Wang, L., Ye, G.-D., Luo, Q., & Chen, Y. (2020) · Theranostics · doi:10.7150/thno.47938 · Cited by 89 · see citing works
Horn, L. A., Riskin, J., Hempel, H., Fousek, K., Lind, H., Hamilton, D. H., McCampbell, K. K., Maeda, D. Y., Zebala, J. A., Su, Z., et al. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2019-000326 · Cited by 88 · see citing works
Self-citationTrials and tribulations of pancreatic cancer immunotherapy
Principe, D. R., Korc, M., Kamath, S. D., Munshi, H. G., & Rana, A. (2021) · Cancer Letters · doi:10.1016/j.canlet.2021.01.031 · Cited by 90 · see citing works
Using human genetics to improve safety assessment of therapeutics
Carss, K., Deaton, A. M., Río-Espínola, A. D., Diogo, D., Fielden, M. R., Kulkarni, D. A., Moggs, J. G., Newham, P., Nelson, M. R., Sistare, F. D., et al. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00561-w · Cited by 88 · see citing works
TGFβ Signaling in the Pancreatic Tumor Microenvironment
Principe, D. R., Timbers, K. E., Atia, L. G., Koch, R. M., & Rana, A. (2021) · Cancers · doi:10.3390/cancers13205086 · Cited by 86 · see citing works
Gautam, S. K., Batra, S. K., & Jain, M. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01813-y · Cited by 88 · see citing works
Tumor microenvironment and immunotherapy for triple-negative breast cancer
Guo, Z.-J., Zhu, Z.-Y., Lin, X.-X., Wang, S., Wen, Y.-H., Wang, L.-B., Zhi, L.-L., & Zhou, J.-C. (2024) · Biomarker Research · doi:10.1186/s40364-024-00714-6 · Cited by 84 · see citing works
Okusaka, T., & Furuse, J. (2020) · Journal of Gastroenterology · doi:10.1007/s00535-020-01666-y · Cited by 85 · see citing works
Facts and Hopes in Immunotherapy of Pancreatic Cancer
Bockorny, B., Grossman, J. E., & Hidalgo, M. M. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-3452 · Cited by 86 · see citing works
Metropulos, A. E., Munshi, H. G., & Principe, D. R. (2022) · eBioMedicine · doi:10.1016/j.ebiom.2022.104380 · Cited by 81 · see citing works
Immunomodulation to enhance the efficacy of an HPV therapeutic vaccine
Rumfield, C. S., Pellom, S. T., Morillon, Y. M., Schlom, J., & Jochéms, C. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-000612 · Cited by 80 · see citing works
Self-citationThe state of the art of bispecific antibodies for treating human malignancies
Wang, S., Chen, K., Lei, Q., Ma, P., Yuan, A. Q., Zhao, Y. J., Jiang, Y., Hong, F., Xing, S., Fang, Y., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202114291 · Cited by 82 · see citing works
Ni, J., Zhang, Z., Ge, M.-J., Chen, J., & Zhuo, W. (2022) · Acta Pharmacologica Sinica · doi:10.1038/s41401-022-00953-z · Cited by 84 · see citing works
Liu, D., Zhou, J., Wang, Y., Li, M., Jiang, H., Liu, Y., Yin, X., Ge, M., Xiang, X., Ying, J., et al. (2022) · BMC Medicine · doi:10.1186/s12916-022-02605-9 · Cited by 79 · see citing works
The strategies to cure cancer patients by eradicating cancer stem-like cells
Mai, Y., Su, J., Yang, C., Xia, C., & Fu, L. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01867-y · Cited by 78 · see citing works
Therapeutic strategies to remodel immunologically cold tumors
Wang, M., Wang, S., Desai, J., Trapani, J. A., & Neeson, P. J. (2020) · Clinical & Translational Immunology · doi:10.1002/cti2.1226 · Cited by 77 · see citing works
Cheng, B., Ding, K., Chen, P., Ji, J., Luo, T., Guo, X., Qiu, W., Ma, C., Meng, X., Wang, J., et al. (2022) · 癌症：英文版 · doi:10.1002/cac2.12244 · Cited by 76 · see citing works
Immune checkpoint inhibitors in colorectal cancer: limitation and challenges
Yan, S., Wang, W., Feng, Z., Xue, J., Liang, W., Wu, X., Tan, Z., Zhang, X., Zhang, S., Li, X., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1403533 · Cited by 77 · see citing works
Therapeutic targeting of TGF-β in cancer: hacking a master switch of immune suppression
van den Bulk, J., de Miranda, N. F. C. C., & ten Dijke, P. (2021) · Clinical Science · doi:10.1042/cs20201236 · Cited by 75 · see citing works
Collins, J. M., Redman, J. M., & Gulley, J. L. (2018) · Expert Review of Vaccines · doi:10.1080/14760584.2018.1506332 · Cited by 73 · see citing works
Self-citationBu, M. T., Chandrasekhar, P., Ding, L., & Hugo, W. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108211 · Cited by 72 · see citing works
Advances in Diagnosis and Therapy for Bladder Cancer
Hu, X., Li, G., & Wu, S. (2022) · Cancers · doi:10.3390/cancers14133181 · Cited by 73 · see citing works
- Authors
- Strauss, J., Heery, C. R., Schlom, J., Madan, R. A., Cao, L., Kang, Z., Lamping, E., Marté, J. L., Donahue, R. N., Grenga, I., Cordes, L., Christensen, O., Mahnke, L., Helwig, C., & Gulley, J. L.
- Affiliations
- National Institutes of Health (US)
- 7EMD Serono, Billerica, Massachusetts.
- Merck KGaA, Darmstadt (Germany) (DE)
- Corresponding author
- Gulley, James L.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2018-03-14
- Volume
- 24
- Issue
- 6
- Pages
- 1287-1295
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC7985967
- OpenAlex
- W2781947653
- Cited by
- 406
- References
- 35
- Citations by year
- 2026: 22 · 2025: 29 · 2024: 48 · 2023: 40 · 2022: 81 · 2021: 73 · 2020: 64 · 2019: 26 · 2018: 20 · 2017: 3
- FWCI
- 17.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (HHSN261200800001C)
- National Cancer Institute (HHSN261200800001E), ZIABC010945)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- bifunctional fusion protein, PD-L1, TGF-β trap, TGF-β1, TGF-beta2, TGF-beta3, advanced solid tumors, maximum tolerated dose, safety, pharmacokinetics, immunogenicity, cervical cancer, pancreatic cancer, anal cancer, carcinoid tumor, dose escalation
- MeSH terms
- Antineoplastic Agents, Immunological, Adult, Aged, Combined Modality Therapy, Female, Humans, Male, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Neoplasms, Transforming Growth Factor beta, Treatment Outcome, Antibodies, Bispecific, Retreatment, Molecular Targeted Therapy, B7-H1 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
