Tumor Regression and Delayed Onset Toxicity Following B7-H4 CAR T Cell Therapy
Open accessAbstract
B7-H4 protein is frequently overexpressed in ovarian cancer. Here, we engineered T cells with novel B7-H4-specific chimeric antigen receptors (CARs) that recognized both human and murine B7-H4 to test the hypothesis that B7-H4 CAR T cell therapy can be applied safely in preclinical models. B7-H4 CAR T cells specifically secreted IFN-γ and lysed B7-H4(+) targets. In vivo, B7-H4 CAR T cells displayed antitumor reactivity against B7-H4(+) human ovarian tumor xenografts. Unexpectedly, B7-H4 CAR T cell treatment reproducibly showed delayed, lethal toxicity 6-8 weeks after therapy. Comprehensive assessment of murine B7-H4 protein distribution uncovered expression in ductal and mucosal epithelial cells in normal tissues. Postmortem analysis revealed the presence of widespread histologic lesions that correlated with B7-H4(+) expression, and were inconsistent with graft versus host disease. Lastly, expression patterns of B7-H4 protein in normal human tissue were comparable to distribution in mice, advancing our understanding of B7-H4. We conclude that B7-H4 CAR therapy mediates control of cancer outgrowth. However, long-term engraftment of B7-H4 CAR T cells mediates lethal, off-tumor toxicity that is likely due to wide expression of B7-H4 in healthy mouse organs. This model system provides a unique opportunity for preclinical evaluation of safety approaches that limit CAR-mediated toxicity after tumor destruction in vivo.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Delayed toxicity is associated with changes in gene expression, which can affect the expression of downstream genes.
“What underlay their success was the fact that delayed toxicity is associated with changes in gene expression, which can, in turn, affect the expression of downstream genes [134,135].”
From Machine Learning Based Toxicity Prediction: From Chemical Structural Description to Transcriptome Analysis (2018) · cites this paper as [135]
Cites
Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia
Maude, S. L., Frey, N., Shaw, P. A., Aplenc, R., Barrett, D. M., Bunin, N. J., Chew, A., Gonzalez, V. E., Zheng, Z., Lacey, S. F., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1407222 · Cited by 5,413 · see citing works
Chimeric antigen receptor–modified T cells in chronic lymphoid leukemia
Porter, D. L., Levine, B. L., Kalos, M., Bagg, A., & June, C. H. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103849 · Cited by 3,565 · see citing works
Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia
Grupp, S. A., Kalos, M., Barrett, D., Aplenc, R., Porter, D. L., Rheingold, S. R., Teachey, D. T., Chew, A., Hauck, B., Wright, J. F., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1215134 · Cited by 3,509 · see citing works
Morgan, R. A., Yang, J. C.-H., Kitano, M., Dudley, M. E., Laurençot, C. M., & Rosenberg, S. A. (2010) · Molecular Therapy · doi:10.1038/mt.2010.24 · Cited by 2,542 · see citing works
Gross, G., Waks, T., & Eshhar, Z. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.24.10024 · Cited by 1,597 · see citing works
Therapeutic antibodies: successes, limitations and hopes for the future
Chames, P., Van Regenmortel, M., Weiss, E., & Baty, D. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00190.x · Cited by 1,382 · see citing works
Milone, M. C., Fish, J. D., Carpenito, C., Carroll, R. G., Binder, G. K., Teachey, D., Samanta, M., Lakhal, M., Gloss, B., Danet-Desnoyers, G., et al. (2009) · Molecular Therapy · doi:10.1038/mt.2009.83 · Cited by 1,197 · see citing works
B7-H4, a Molecule of the B7 Family, Negatively Regulates T Cell Immunity
Sica, G., Choi, I.-H., Zhu, G., Tamada, K., Wang, S.-D., Tamura, H., Chapoval, A. I., Flies, D. B., Bajorath, J., & Chen, L. (2003) · Immunity · doi:10.1016/s1074-7613(03)00152-3 · Cited by 709 · see citing works
Wang, L.-C. S., Lo, A., Scholler, J., Sun, J., Majumdar, R. S., Kapoor, V., Antzis, M., Cotner, C. E., Johnson, L. A., Durham, A. C., et al. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0027 · Cited by 653 · see citing works
Design and development of therapies using chimeric antigen receptor‐expressing T cells
Dotti, G., Gottschalk, S. M., Savoldo, B., & Brenner, M. K. (2013) · Immunological Reviews · doi:10.1111/imr.12131 · Cited by 510 · see citing works
Latest research and treatment of advanced-stage epithelial ovarian cancer
Coleman, R. L., Monk, B. J., Sood, A. K., & Herzog, T. J. (2013) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2013.5 · Cited by 489 · see citing works
Tran, E., Chinnasamy, D., Yu, Z., Morgan, R. A., Lee, C. R., Restifo, N. P., & Rosenberg, S. A. (2013) · The Journal of Experimental Medicine · doi:10.1084/jem.20130110 · Cited by 467 · see citing works
Zhao, Y., Moon, E. K., Carpenito, C., Paulos, C. M., Liu, X., Brennan, A. L., Chew, A., Carroll, R. G., Scholler, J., Levine, B. L., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-2880 · Cited by 448 · see citing works
B7S1, a Novel B7 Family Member that Negatively Regulates T Cell Activation
Prasad, D. V. R., Richards, S., Muoi, X., & Dong, C. (2003) · Immunity · doi:10.1016/s1074-7613(03)00147-x · Cited by 431 · see citing works
B7x: A widely expressed B7 family member that inhibits T cell activation
Zang, X., Loke, P., Kim, J., MURPHY, K. M. M., Waitz, R., & Allison, J. P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1434299100 · Cited by 401 · see citing works
King, M. A., Covassin, L., Brehm, M. A., Racki, W. J., Pearson, T., Leif, J., Laning, J. C., Fodor, W. L., Foreman, O., Burzenski, L. M., et al. (2009) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2009.03933.x · Cited by 389 · see citing works
CD27 costimulation augments the survival and antitumor activity of redirected human T cells in vivo
Song, D.-G., Ye, Q., Poussin, M., Pritchard, G. H., Figini, M., & Powell, D. J. (2011) · Blood · doi:10.1182/blood-2011-03-344275 · Cited by 355 · see citing works
Beilhack, A., Schulz, S., Baker, J. B., Beilhack, G. F., Wieland, C. B., Herman, E. I., Baker, E. M., Cao, Y., Contag, C. H., & Negrin, R. S. (2005) · Blood · doi:10.1182/blood-2005-02-0509 · Cited by 352 · see citing works
Lanitis, E., Poussin, M., Klattenhoff, A. W., Song, D.-G., Sandaltzopoulos, R., June, C. H., & Powell, D. J. (2013) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-13-0008 · Cited by 329 · see citing works
Frigault, M. J., Lee, J., Basil, M. C., Carpenito, C., Motohashi, S., Scholler, J., Kawalekar, O. U., Guedan, S., McGettigan, S. E., Posey, A. D., et al. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0186 · Cited by 324 · see citing works
Miotti, S., Canevari, S., Ménard, S., Mezzanzanica, D., Porro, G. A., Pupa, S. M., Regazzoni, M., Tagliabue, E., & COLNAGHI, M. I. (1987) · International Journal of Cancer · doi:10.1002/ijc.2910390306 · Cited by 315 · see citing works
Ritprajak, P., & Azuma, M. (2014) · Oral Oncology · doi:10.1016/j.oraloncology.2014.11.014 · Cited by 314 · see citing works
Blat, D., Zigmond, E., Alteber, Z., Waks, T., & Eshhar, Z. (2014) · Molecular Therapy · doi:10.1038/mt.2014.41 · Cited by 246 · see citing works
Choi, I.-H., Zhu, G., Sica, G., Strome, S. E., Cheville, J. C., Lau, J. S., Zhu, Y., Flies, D. B., Tamada, K., & Chen, L. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.9.4650 · Cited by 244 · see citing works
Salceda, S., Tang, T., Kmet, M., Munteanu, A. I., Ghosh, M., Macina, R. A., Liu, W., Pilkington, G. R., & Papkoff, J. (2005) · Experimental Cell Research · doi:10.1016/j.yexcr.2005.01.018 · Cited by 215 · see citing works
Kakarla, S., & Gottschalk, S. M. (2014) · The Cancer Journal · doi:10.1097/ppo.0000000000000032 · Cited by 192 · see citing works
Lanitis, E., Poussin, M., Hagemann, I. S., Coukos, G., Sandaltzopoulos, R., Scholler, N., & Powell, D. J. (2011) · Molecular Therapy · doi:10.1038/mt.2011.256 · Cited by 187 · see citing works
van Rijn, R. S., Simonetti, E. R., Hagenbeek, A., Hogenes, M. C. H., de Weger, R. A., van Dijk, M. R., Weijer, K. C., Spits, H., Storm, G., van Bloois, L., et al. (2003) · Blood · doi:10.1182/blood-2002-10-3241 · Cited by 186 · see citing works
In vivo imaging of graft-versus-host-disease in mice
Panoskaltsis‐Mortari, A., Price, A., Hermanson, J. R., Taras, E. P., Lees, C. J., Serody, J. S., & Blazar, B. R. (2004) · Blood · doi:10.1182/blood-2003-08-2827 · Cited by 150 · see citing works
B7-H4 overexpression in ovarian tumors
Tringler, B., Liu, W., Corral, L. G., Torkko, K. C., Enomoto, T., Davidson, S. A., Lucia, M. S., Heinz, D. E., Papkoff, J., & Shroyer, K. R. (2005) · Gynecologic Oncology · doi:10.1016/j.ygyno.2005.08.060 · Cited by 148 · see citing works
Quandt, D., Fiedler, E., Boettcher, D., Marsch, W. C., & Seliger, B. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2268 · Cited by 135 · see citing works
Laniti, D. D., Lanitis, E., Zhao, A., Joshi, S., Cheng, Y., Sandaltzopoulos, R., Ra, H.-J., Danet-Desnoyers, G. A., Powell, D. J., & Scholler, N. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-3457 · Cited by 118 · see citing works
The B7 family of immunoregulatory receptors: A comparative and evolutionary perspective
Hansen, J. D., Pasquier, L. D., Lefranc, M., Lopez, V., Benmansour, A., & Boudinot, P. (2008) · Molecular Immunology · doi:10.1016/j.molimm.2008.10.007 · Cited by 113 · see citing works
Zhang, L., Wu, H., Lu, D., Li, G., Sun, C., Song, H., Li, J., Zhai, T., Huang, L., Hou, C., et al. (2013) · Oncogene · doi:10.1038/onc.2012.600 · Cited by 105 · see citing works
Azuma, T., Zhu, G., Xu, H., Rietz, A. C., Drake, C. G., Matteson, E. L., & Chen, L. (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000166 · Cited by 80 · see citing works
B7-H4–deficient mice display augmented neutrophil-mediated innate immunity
Zhu, G., Augustine, M. M., Azuma, T., Luo, L., Yao, S., Anand, S., Rietz, A. C., Huang, J., Xu, H., Flies, A. S., et al. (2008) · Blood · doi:10.1182/blood-2008-01-133223 · Cited by 80 · see citing works
Generation and Characterization of B7-H4/B7S1/B7x-Deficient Mice
Suh, W., Wang, S., Duncan, G. S., Miyazaki, Y., Cates, E. C., Walker, T. D., Gajewska, B., Deenick, E. K., Dawicki, W., Okada, H., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00755-06 · Cited by 76 · see citing works
Structure and Cancer Immunotherapy of the B7 Family Member B7x
Jeon, H., Vigdorovich, V. I., Garrett-Thomson, S. C., Janakiram, M., Ramagopal, U. A., Abadi, Y. M., Lee, J. S., Scandiuzzi, L., Ohaegbulam, K. C., Chinai, J. M., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.09.053 · Cited by 76 · see citing works
VanSeggelen, H., Hammill, J. A., Dvorkin‐Gheva, A., Tantalo, D. G. M., Kwiecień, J. M., Denisova, G. F., Rabinovich, B. A., Wan, Y., & Bramson, J. L. (2015) · Molecular Therapy · doi:10.1038/mt.2015.119 · Cited by 75 · see citing works
Nervi, B., Rettig, M. P., Ritchey, J., Wang, H. L., Bauer, G., Walker, J. E., Bonyhadi, M. L., BERENSON, R. J., Prior, J. L., Piwnica-Worms, D. R., et al. (2007) · Experimental Hematology · doi:10.1016/j.exphem.2007.06.007 · Cited by 74 · see citing works
NKG2D CAR T‐cell therapy inhibits the growth of NKG2D ligand heterogeneous tumors
Spear, P., Barber, A. E., Rynda‐Apple, A., & Sentman, C. L. (2013) · Immunology and Cell Biology · doi:10.1038/icb.2013.17 · Cited by 71 · see citing works
Host B7x Promotes Pulmonary Metastasis of Breast Cancer
Abadi, Y. M., Jeon, H., Ohaegbulam, K. C., Scandiuzzi, L., Ghosh, K., Hofmeyer, K. A., Lee, J. S., Ray, A., Gravekamp, C., & Zang, X. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202439 · Cited by 69 · see citing works
Tissue-specific expression of B7x protects from CD4 T cell–mediated autoimmunity
Wei, J., Loke, P., Zang, X., & Allison, J. P. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20100639 · Cited by 66 · see citing works
B7-H4 as a potential target for immunotherapy for gynecologic cancers: A closer look
Smith, J. B., Stashwick, C., & Powell, D. J. (2014) · Gynecologic Oncology · doi:10.1016/j.ygyno.2014.03.553 · Cited by 65 · see citing works
B7-H4 Expression Promotes Tumorigenesis in Ovarian Cancer
Cheng, L., Jiang, J., Gao, R., Wei, S., Nan, F., Li, S., & Kong, B. (2009) · International Journal of Gynecological Cancer · doi:10.1111/igc.0b013e3181ad0fa2 · Cited by 64 · see citing works
An Anti-B7-H4 Antibody–Drug Conjugate for the Treatment of Breast Cancer
Leong, S. R., Liang, W., Wu, Y., Crocker, L., Cheng, E., Sampath, D., Ohri, R. V., Raab, H. E., Hass, P. E., Pham, T., et al. (2015) · Molecular Pharmaceutics · doi:10.1021/mp5007745 · Cited by 62 · see citing works
B7-H4 Expression by Nonhematopoietic Cells in the Tumor Microenvironment Promotes Antitumor Immunity
Rahbar, R., Lin, A., Ghazarian, M., Yau, H. L., Paramathas, S., Lang, P. A., Schildknecht, A., Elford, A. R., Garcia-Batres, C. R., Martin, B. G., et al. (2014) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0113 · Cited by 47 · see citing works
Kreymborg, K., Haak, S., Murali, R., Wei, J., Waitz, R., Gasteiger, G., Savage, P. A., van den Brink, M. R. M., & Allison, J. P. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0100 · Cited by 39 · see citing works
B7x in the Periphery Abrogates Pancreas-Specific Damage Mediated by Self-reactive CD8 T Cells
Lee, J. S., Scandiuzzi, L., Ray, A., Wei, J., Hofmeyer, K. A., Abadi, Y. M., Loke, P., Lin, J., Yuan, J. D., SERREZE, D. V., et al. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1201241 · Cited by 34 · see citing works
Leung, J., & Suh, W. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1201242 · Cited by 26 · see citing works
Tissue-Expressed B7x Affects the Immune Response to and Outcome of Lethal Pulmonary Infection
Hofmeyer, K. A., Scandiuzzi, L., Ghosh, K., Pirofski, L., & Zang, X. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200701 · Cited by 24 · see citing works
B7-H4 Expression in Normal and Diseased Human Islet β Cells
Cheung, S. S. C., Ou, D., Metzger, D. L., Meloche, M. R., Ao, Z., Ng, S. S. W., Owen, D., & Warnock, G. L. (2013) · Pancreas · doi:10.1097/mpa.0b013e31829695d2 · Cited by 19 · see citing works
Strain-dependent Lethal Toxicity in NKG2D Ligand-targeted CAR T-cell Therapy
Lynn, R. C., & Powell, D. J. (2015) · Molecular Therapy · doi:10.1038/mt.2015.162 · Cited by 16 · see citing works
Isolation and Validation of Anti-B7-H4 scFvs from an Ovarian Cancer scFv Yeast-Display Library
Laniti, D. D., & Scholler, N. (2015) · Methods in molecular biology · doi:10.1007/978-1-4939-2748-7_2 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours
Flugel, C. L., Majzner, R. G., Krenciute, G., Dotti, G., Riddell, S. R., Wagner, D. L., & Abou‐El‐Enein, M. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00704-3 · Cited by 571 · see citing works
CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape
Rodríguez-García, A., Palazón, A., Noguera-Ortega, E., Powell, D. J., & Guedan, S. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01109 · Cited by 317 · see citing works
The third group of the B7‐ CD 28 immune checkpoint family: HHLA 2, TMIGD 2, B7x, and B7‐H3
Janakiram, M., Shah, U. A., Liu, W., Zhao, A., Schoenberg, M., & Zang, X. (2017) · Immunological Reviews · doi:10.1111/imr.12521 · Cited by 225 · see citing works
Wu, Y., & Wang, G. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19082358 · Cited by 193 · see citing works
B7-H4, a promising target for immunotherapy
Wang, J., & Wang, W. (2019) · Cellular Immunology · doi:10.1016/j.cellimm.2019.104008 · Cited by 101 · see citing works
MacGregor, H. L., Sayad, A., Elia, A., Wang, B. X., Katz, S. R., Shaw, P. A., Clarke, B. A., Crome, S. Q., Robert-Tissot, C., Bernardini, M. Q., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0816-5 · Cited by 78 · see citing works
A T-cell–engaging B7-H4/CD3-bispecific Fab-scFv Antibody Targets Human Breast Cancer
Iizuka, A., Nonomura, C., Ashizawa, T., Kondou, R., Ohshima, K., Sugino, T., Mitsuya, K., Hayashi, N., Nakasu, Y., Maruyama, K., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-3123 · Cited by 77 · see citing works
Molecular Pathways: Evaluating the Potential for B7-H4 as an Immunoregulatory Target
MacGregor, H. L., & Ohashi, P. S. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2440 · Cited by 75 · see citing works
The B7x Immune Checkpoint Pathway: From Discovery to Clinical Trial
John, P., Yao, W., Liu, W., Du, M., Guan, F., & Zang, X. (2019) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2019.09.008 · Cited by 71 · see citing works
Minutolo, N. G., Sharma, P., Poussin, M., Shaw, L. C., Brown, D. P., Hollander, E. E., Smole, A., Rodríguez-García, A., Hui, J. Z., Zappala, F., et al. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.9b11622 · Cited by 70 · see citing works
John, P., Pulanco, M. C., Galbo, P. M., Yao, W., Ohaegbulam, K. C., Zheng, D., & Zang, X. (2022) · Nature Communications · doi:10.1038/s41467-022-30143-8 · Cited by 43 · see citing works
CAR-macrophage versus CAR-T for solid tumors: The race between a rising star and a superstar
Chen, K., Liu, M., Wang, J., & Fang, S. (2023) · Biomolecules and Biomedicine · doi:10.17305/bb.2023.9675 · Cited by 45 · see citing works
Toader, D., Fessler, S. P., Collins, S. D., Conlon, P. R., Bollu, R., Catcott, K. C., Chin, C., Dirksen, A., Du, B., Duvall, J. R., et al. (2023) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-22-0786 · Cited by 41 · see citing works
Najafi, S., & Mortezaee, K. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.122387 · Cited by 39 · see citing works
Immune checkpoints and cancer immunotherapies: insights into newly potential receptors and ligands
Kamali, A. N., Bautista, J. M., Eisenhut, M., & Hamedifar, H. (2023) · Therapeutic Advances in Vaccines and Immunotherapy · doi:10.1177/25151355231192043 · Cited by 38 · see citing works
Development of T-cell engagers selective for cells co-expressing two antigens
DiCara, D. M., Bhakta, S., Go, M. A. T., Ziai, J. M., Firestein, R., Forrest, B., Gu, C., Leong, S. R., Lee, G., Yu, S., et al. (2022) · mAbs · doi:10.1080/19420862.2022.2115213 · Cited by 24 · see citing works
Zhu, Y., Chen, J., Liu, Y., Zheng, X. W., Feng, J., Chen, X., Jiang, T., Li, Y., Zhang, J., & Chen, L. (2022) · Pathology - Research and Practice · doi:10.1016/j.prp.2022.153911 · Cited by 23 · see citing works
Vaishnav, J., Khan, F., Yadav, M., PARMAR, N. R., Buch, H., Jadeja, S. D., Dwivedi, M., & Begum, R. (2022) · Immunobiology · doi:10.1016/j.imbio.2022.152274 · Cited by 22 · see citing works
CAR-Based Immunotherapy of Solid Tumours—A Survey of the Emerging Targets
Maher, J. F., & Davies, D. M. (2023) · Cancers · doi:10.3390/cancers15041171 · Cited by 22 · see citing works
Hammill, J. A., Kwiecień, J. M., Dvorkin‐Gheva, A., Lau, V. W. C., Baker, C. L., Wu, Y., Bezverbnaya, K., Aarts, C. W., Heslen, C. W., Denisova, G. F., et al. (2020) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2020.04.001 · Cited by 19 · see citing works
CAR-T Cells Targeting Immune Checkpoint Pathway Players
Golubovskaya, V. (2022) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2704121 · Cited by 19 · see citing works
B7H4 Role in Solid Cancers: A Review of the Literature
Dawidowicz, M., Kot, A., Mielcarska, S., Psykała, K., Kula, A., Waniczek, D., & Świętochowska, E. (2024) · Cancers · doi:10.3390/cancers16142519 · Cited by 18 · see citing works
Kaur, G., & Janakiram, M. (2019) · ESMO Open · doi:10.1136/esmoopen-2019-000554 · Cited by 18 · see citing works
Li, Y., Chen, G.-L., Xiang, Z., Liu, Y., Li, X., Bi, J.-W., & Wang, Q. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114648 · Cited by 18 · see citing works
Eltoukhy, H. S., Sinha, G., Moore, C. A., Sandiford, O. A., & Rameshwar, P. (2017) · Cellular Immunology · doi:10.1016/j.cellimm.2017.07.011 · Cited by 13 · see citing works
Chapoval, A. I., Chapoval, S. P., Shcherbakova, N. S., & Щербаков, Д. Н. (2019) · Russian Journal of Bioorganic Chemistry · doi:10.1134/s1068162019050091 · Cited by 12 · see citing works
Lv, C., Han, S., Wu, B., Liang, Z., Li, Y., Zhang, Y., Lang, Q., Zhong, C., Fu, L., Yu, Y. W., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.984172 · Cited by 12 · see citing works
Dawidowicz, M., Kula, A., Mielcarska, S., Kiczmer, P., Skiba, H., Krygier, M., Chrabańska, M., Piecuch, J., Szrot, M., Robotycka, J., et al. (2023) · Cells · doi:10.3390/cells12060861 · Cited by 12 · see citing works
Chand, D., Dhawan, D., Sankin, A. I., Ren, X., Lin, J., Schoenberg, M., Knapp, D. W., & Zang, X. (2019) · Bladder Cancer · doi:10.3233/blc-180204 · Cited by 12 · see citing works
The role of B7-H4 in ovarian cancer immunotherapy: current status, challenges, and perspectives
Zhou, L., Duan, Y., Fu, K., Zhang, M., Li, K., & Yin, R. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1426050 · Cited by 11 · see citing works
SJI 2020 special issue: A catalogue of Ovarian Cancer targets for CAR therapy
Benard, E., Casey, N. P., Inderberg, E. M., & Wälchli, S. (2020) · Scandinavian Journal of Immunology · doi:10.1111/sji.12917 · Cited by 12 · see citing works
Pagnotti, G. M., Atkinson, R. M., Romeiser, J. L., Akalin, A., Korman, M., & Shroyer, K. R. (2017) · Applied immunohistochemistry & molecular morphology · doi:10.1097/pai.0000000000000608 · Cited by 11 · see citing works
Prospects and challenges of CAR-T in the treatment of ovarian cancer
Chen, B., & Liu, J. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112112 · Cited by 10 · see citing works
Sankin, A. I., Narasimhulu, D. M., John, P., Gartrell, B. A., Schoenberg, M., & Zang, X. (2017) · Urologic Oncology Seminars and Original Investigations · doi:10.1016/j.urolonc.2017.04.007 · Cited by 10 · see citing works
Innovative approaches to CAR-T cell therapy: the role of lipid metabolism pathways
Guo, M., Zhang, Y., Yuan, X. H., & Wang, X. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06718-6 · Cited by 9 · see citing works
Role of B7 family members in glioma: Promising new targets for tumor immunotherapy
Wang, Y., Li, M., Wang, G., & Wu, H. M. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2022.1091383 · Cited by 8 · see citing works
Chen, C., Qu, Q., Xie, F., Zhu, W., Zhu, Y., & Huang, J. (2017) · BMC Cancer · doi:10.1186/s12885-017-3615-8 · Cited by 8 · see citing works
Depleting Tumor Cells Expressing Immune Checkpoint Ligands—A New Approach to Combat Cancer
Marcucci, F., & Rumio, C. (2021) · Cells · doi:10.3390/cells10040872 · Cited by 8 · see citing works
B7 Family Members in Pancreatic Ductal Adenocarcinoma: Attractive Targets for Cancer Immunotherapy
Chen, X., Li, J., Chen, Y., Que, Z., Du, J., & Zhang, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315005 · Cited by 6 · see citing works
Chimeric antigen receptor T cell immunotherapy for gynecological malignancies
Gao, Y., He, J. N., Wang, J., Xu, H., & Ma, L. (2025) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2025.104680 · Cited by 5 · see citing works
Kang, N., Xue, H., Wong, N. K. Y., Lin, Y., Classen, A., Wu, R., Oo, H. Z., Dong, X., Trinh, A. M., Lin, D., et al. (2025) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-24-0958 · Cited by 4 · see citing works
Abayasiriwardana, K. S., Wu, L., Laklai, H., Nocula‐Ługowska, M., Tchistiakova, L., Narula, J., Jackson-Fisher, A. J., Golas, J., Lam, M., Grinstein, V., et al. (2025) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-24-0379 · Cited by 4 · see citing works
Vaishnav, J., Jadeja, S. D., Singh, M., Khan, F., Yadav, M., & Begum, R. (2022) · Immunological Investigations · doi:10.1080/08820139.2022.2097091 · Cited by 4 · see citing works
B7-H4: a multifaceted immune checkpoint and oncoprotein in cancer biology and immunotherapy
Zhang, C., Miao, Z., Cao, J., Wang, X., & Shi, T. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1837397 · Cited by 3 · see citing works
Pre-clinical efficacy of CD20-targeted chimeric antigen receptor T cells for non-Hodgkin's lymphoma
Wen, H., Lou, X., Qu, Z., Qin, C., Jiang, H., Yang, Y., Kang, L., Geng, X., Yu, L., & Huang, Y. (2022) · Discover Oncology · doi:10.1007/s12672-022-00588-w · Cited by 3 · see citing works
Li, W., Zhou, M., Wang, L., Huang, L., Chen, X., Sun, X., & Liu, T. (2023) · Cancer Innovation · doi:10.1002/cai2.95 · Cited by 3 · see citing works
Next generation immune checkpoints
Perez, N. M., Moziak, K., & Martin, A. M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-14064-8.90009-2 · Cited by 1 · see citing works
Mammone, R. M., Willis, E., Ruivo, P., Finesso, G., Cox, A., Assenmacher, C., Radaelli, E., Piersigilli, A., & Miranda, I. C. (2026) · Veterinary Pathology-Supplement · doi:10.1177/03009858251409216 · Cited by 1 · see citing works
Dutsch-Wicherek, M. M., Lazar, A., Tomaszewska, R., Kliś, K. M., Dziobek, K., & Wicherek, Ł. (2018) · Medical Research Journal · doi:10.5603/mrj.a2018.0022 · Cited by 1 · see citing works
Kulemzin, S. V., Gorchakov, A. A., & Taranin, A. V. (2019) · Cellular Therapy and Transplantation · doi:10.18620/ctt-1866-8836-2019-8-4-19-28 · Cited by 1 · see citing works
Pre-clinical efficacy of CD20-targeted chimeric antigen receptor T cells for non-Hodgkin's lymphomaPreprint
Wen, H., Lou, X., Qu, Z., Qin, C., Jiang, H., Yang, Y., Kang, L., Geng, X., Yu, L., & Huang, Y. (2022) · Research Square · doi:10.21203/rs.3.rs-1916684/v2
Pre-clinical efficacy of CD20-targeted chimeric antigen receptor T cells for non-Hodgkin's lymphomaPreprint
Wen, H., Lou, X., Qu, Z., Qin, C., Jiang, H., Yang, Y., Kang, L., Geng, X., Yu, L., & Huang, Y. (2022) · Research Square · doi:10.21203/rs.3.rs-1916684/v1
Toader, D., Fessler, S. P., Collins, S. D., Conlon, P. R., Bollu, R., Catcott, K. C., Chin, C., Dirksen, A., Du, B., Duvall, J. R., et al. (2023) · doi:10.1158/1535-7163.c.6821443
Toader, D., Fessler, S. P., Collins, S. D., Conlon, P. R., Bollu, R., Catcott, K. C., Chin, C., Dirksen, A., Du, B., Duvall, J. R., et al. (2023) · doi:10.1158/1535-7163.c.6821443.v1
Application and progress of CAR therapy on malignances: from CAR-T to CAR-NK
Zhang, Q. (2024) · MedScien · doi:10.61173/ve5wzw54
WITHDRAWN: Next generation immune checkpoints
Perez, N. M., Moziak, K., & Martin, A. M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-14064-8.00009-6
Developing logic-gated CAR T cells for saferT-cell lymphoma therapy
Bourbon, E. (2025) · theses.fr (ABES) · doi:10.70675/11e2363dzeb1fz46bcza38dz6f6c7aa5545d
B7-H4 in Cancer Immune Evasion and Immunotherapy
Xiao, R., Yu, J., Yan, Y., Kryczek, I., & Zou, W. (2026) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-25-2442
- Authors
- Smith, J. B., Lanitis, E., Dangaj, D., Buza, E., Poussin, M., Stashwick, C., Scholler, N., & Powell, D. J.
- Affiliations
- University of Pennsylvania (US)
- Ludwig Cancer Research (CH)
- Lancaster General Hospital (US)
- SRI International (US)
- Corresponding author
- Powell, Daniel J
- ORCID
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2016-11
- Volume
- 24
- Issue
- 11
- Pages
- 1987-1999
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC5154474
- OpenAlex
- W2478176079
- Cited by
- 58
- References
- 54
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 11 · 2022: 12 · 2021: 1 · 2020: 4 · 2019: 8 · 2018: 2 · 2017: 6
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- Department of Defense (OC110673)
- NIH (RO1-CA168900)
- Immunobiology of Normal and Neoplastic Lymphocytes T32 Training Grant
- NCI (CA016520)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- B7-H4, chimeric antigen receptor T cells, CAR T-cell therapy, ovarian cancer, on-target off-tumor toxicity, tumor regression, IFN-gamma secretion, xenograft models, preclinical safety
- MeSH terms
- Animals, Female, Humans, Ovarian Neoplasms, Receptors, Antigen, T-Lymphocytes, Gene Expression Regulation, Neoplastic, Treatment Outcome, Xenograft Model Antitumor Assays, Cell Line, Tumor, Mice, V-Set Domain-Containing T-Cell Activation Inhibitor 1, Cell- and Tissue-Based Therapy
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