Case report: B7-H3 CAR-T therapy partially controls tumor growth in a basal cell carcinoma patient

Abstract

B7-H3 is over-expressed in multiple types of solid tumors, making it an ideal target for chimeric antigen receptor (CAR)-T therapy. Here, we first report a case of multiple basal cell carcinoma (BCC) patient treated with humanized monoclonal anti-B7-H3 CAR-T cells through direct intratumoral injection. After three dose-escalated injections, the lesion in the abdomen decreased by 40% in volume, shrank from bulging to flat, but was not eradicated completely. The large lesion in the forehead became dry from original ulcer and bleeding. The adverse events observed were itching, myalgia, and redness. Immunohistochemistry analysis demonstrated that B7-H3-positive tumor cells and B7-H3 expression intensity were reduced after injections of CAR-T cells. The number of infiltrating CD3 T cells increased significantly but mainly located outside the tumor region. Subsequently, high levels of TGF-β in the tumor area were observed, suggesting that solid tumor microenvironment may hinder the infiltration and effect of CAR-T cells. In summary, in this particular case report, intratumoral injection of B7-H3 CAR-T cells partially controls tumor growth in the BCC patient with minor adverse events. The efficacy and safety of B7-H3 CAR-T therapy need to be further investigated with a larger cohort of patients. Although only one clinical case is reported here, the anti-B7-H3 CAR-T cell therapy should be considered as a treatment option for solid tumors in the future. This clinical trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) with registration number ChiCTR2100044386.

EpCAM-targeting CAR-T cell immunotherapy is safe and efficacious for epithelial tumors

“…In addition, there is no obvious difference in safety for these two CAR-T cell delivery strategies in the corresponding clinical research (44). Also, the therapeutic potential of local delivery pathways, such as intertumoral injection (45) and intracranial injection (46,47), has been validated in previous studies. Notably, intraventricular administrated IL-13Rα2 CAR-T cells displayed curative efficacy for patient with recurrent multifocal glioblastoma (47), suggesting the therapeutic potential of locally delivered CAR-T cells for specified tumors.…”

TOP CAR with TMIGD2 as a safe and effective costimulatory domain in CAR cells treating human solid tumors

“…Two major considerations of CAR design surround the optimal choice of target antigen and costimulatory domain. Among CAR-T cells targeting solid tumors, B7-H3 has emerged as a uniquely promising target, with all published results from early clinical trials all using second-generation CARs ( 40 – 43 ). In our experiments using in vitro killing assays with lowered transduction efficiency, we found that B7-H3.TMI.ζ CAR-T cells but not other second-generation CAR-T cells could kill three different tumor cell lines.…”

High B7-H3 expression with low PD-L1 expression identifies armored-cold tumors in triple-negative breast cancer

“…However, the biomarkers screening the dominant population benefiting from anti-B7-H3 therapy have not been defined. Several case reports implied that patients with high B7-H3 expression in tumor tissues were more likely to benefit from the anti-B7-H3 treatment 35 , 36 . We reported that TNBC patients with B7-H3 high and PD-L1 low expression face unsatisfactory therapeutic responses, urgently need novel therapies.…”