B7-H3-targeted CAR T cell activity is enhanced by radiotherapy in solid cancers

Marco Ventin; Giulia Cattaneo; Luke Maggs; Jingyu Jia; Shahrzad Arya; Soldano Ferrone; Xinhui Wang; Cristina R Ferrone

doi:10.3389/fonc.2023.1193963

B7-H3-targeted CAR T cell activity is enhanced by radiotherapy in solid cancers

Front Oncol. 2023 Jul 7:13:1193963. doi: 10.3389/fonc.2023.1193963. eCollection 2023.

Authors

Marco Ventin¹, Giulia Cattaneo¹, Luke Maggs¹, Jingyu Jia¹, Shahrzad Arya¹, Soldano Ferrone^{1

2}, Xinhui Wang¹, Cristina R Ferrone³

Affiliations

¹ Division of Gastrointestinal and Oncologic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
² Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.
³ Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA, United States.

Abstract

Adoptive cell therapy utilizing T cells genetically modified to express a chimeric antigen receptor (CAR) has demonstrated promising clinical results in hematological malignancies. However, solid cancers have not seen a similar success due to multiple obstacles. Investigating these escape mechanisms and designing strategies to counteract such limitations is crucial and timely. Growing evidence in the literature supports the hypothesis that radiotherapy has the potential to enhance the susceptibility of solid tumors to CAR T cell therapy, by overcoming mechanisms of resistance. Radiation treatment can increase the susceptibility of different types of solid cancers (TNBC, HNSCC, PDAC) to B7-H3 CAR T cell-mediated eradication. Multiple mechanisms, including reduced cancer cell proliferation, upregulation of the targeted antigen, modulation of apoptotic molecules may contribute to this signal. The information in the literature and the results we describesupport the ability of radiotherapy to improve the efficacy of CAR T cell therapy in solid tumors.

Keywords: B7-H3 CAR T; combinatorial therapy; immunotherapy; radiotherapy; solid cancer.

Grants and funding

This work was supported by grants R01DE028172 (XW), R01CA226981 (XW), Department of Defense Idea Award W81XWH-20-PCRP-IDA (W81XWH2110433) (XW) and National Priorities Research Program of Qatar National Research Fund (NPRP10-0129-170277) (XW), Department of Defense Breakthrough Award Level 2 W81XWH-16-1-0500 (BC190615) (SF), R03CA223886 (SF), R03CA231766 (SF) and Department of Defense Breakthrough Award Level 4 W81XWH-20-1-0315 (BC190615) (SF).