Immunophenotypic transformation in relapsed/refractory mantle cell lymphoma treated with human anti-CD5 chimeric antigen receptor T cells: A Case Report

Abstract

Relapsed/refractory (R/R) mantle cell lymphoma (MCL) with primary drug resistance to Bruton tyrosine kinase inhibitor and mutated TP53 responds poorly to conventional treatments. Chimeric antigen receptor (CAR) T cell therapy has emerged as one of the most effective treatments for R/R B cell lymphoma. However, no reports of CD5 CAR T cell treatment for MCL have been reported. In this paper, we report a R/R MCL patient with primary drug resistance to BTK inhibitors and TP53 mutation enrolled in a human CD5 CAR T cell trial. Remission of the primary disease was observed half a month after CAR T cell infusion. However, ascites was observed 2 weeks later. Flow cytometry suggested disease progression and immunophenotypic transformation. CD5 in CAR T cells turned negative and the expression of CD38 was enhanced. The patient was treated with a combination of daratumumab and Gemox (gemcitabine + oxaliplatin), abdominal distension and pain were markedly reduced, and ascites disappeared. We report the first case of human CD5 CAR T cell treatment for a patient with R/R MCL, providing insight on treatment strategies for such patients.

CD5 blockade, a novel immune checkpoint inhibitor, enhances T cell anti-tumour immunity and delays tumour growth in mice harbouring poorly immunogenic 4T1 breast tumour homografts

“…CD5 has been targeted as a tumour antigen expressed by nonsolid tumours using depleting, toxin-conjugated anti-CD5 Mab (6)(7)(8)(9)(10)(11)(12)34) and most recently by using CD5 CAR T cells (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)35). It is also upregulated during human T cell activation and negatively regulates the T cell receptor on cytotoxic T cells, limiting their ability to recognize poorly immunogenic tumour antigens (2).…”

“…Therefore, it has been used as a targetable tumour antigen for T and B cell malignancies (5). Several passive and active immunotherapeutic approaches have implemented t he use of anti-CD5 immunoconjugates linked to cytotoxic molecules (6)(7)(8)(9)(10)(11)(12) and CD5 CAR T cells (13)(14)(15)(16)(17)(18)(19)(20)(21)(22) to treat CD5 + hematologic malignancies.…”