We developed a third-generation chimeric antigen receptor (CAR) targeting ICAM-1 to leverage adoptive T-cell therapy as a new treatment modality.<b>Experimental Design:</b> ICAM-1 CAR T cells were applied to multiple malignant and nonmalignant target cells to investigate specific target cell death and "off-tumor" toxicity <i>in vitro</i><i>In vivo</i> therapeutic efficacy of ICAM-1 CAR T cells was examined in ATC mouse models established from a cell line and patient-derived tumors that rapidly develop systemic metastases.<b>Results:</b> ICAM-1 CAR T cells demonstrated robust and specific killing of PTC and ATC cell lines <i>in vitro</i> Interestingly, although certain ATC cell lines showed heterogeneous levels of ICAM-1 expression, addition of cytotoxic CAR T cells induced increased ICAM-1 expression such that all cell lines became targetable.
In this study, we investigated CAR-T therapy targeting carcino-embryonic antigen (CEA)-positive colorectal cancer (CRC) patients with metastases to evaluate its safety and efficacy.
Expert commentary: While some recent studies have shown promising results, the ultimate success of CAR-T therapies in solid tumor patients will require the following improvements to clinical regimens: (1) local delivery of CAR-T cells; (2) combination of CAR-T cells with chemotherapeutic drugs to treat metastatic tumors; (3) combination of CAR-T with immune checkpoint inhibitors; (4) combination therapy using CAR-T cells targeting two different antigens; and (5) the use of CAR-T as a strategy to prevent tumor recurrence and metastasis after radical resection.
Mouse and human T cells were engineered to express a chimeric antigen receptor (CAR) targeted against VEGFR-2, which is overexpressed in tumor vasculature and is responsible for VEGF-mediated tumor progression and metastasis.