The combination of cyclophosphamide and human T cells genetically engineered to target CD19 can eradicate established B-cell lymphoma.

Abstract

T cells genetically engineered to express tumour-targeting receptors are attractive anti-cancer therapeutic agents. Human T cells engrafted with a chimeric receptor specific for the B-cell lymphoma antigen CD19 fused to the CD3zeta receptor (aCD19z) are functional in vitro. Current successful clinical protocols targeting melanoma use pre-conditioning chemotherapy in combination with T cells. This study demonstrated that interleukin-2 expanded aCD19z T cells combined with cyclophosphamide effectively treated five-day established Raji B-cell lymphoma in an immunocompromised model system with 50% of mice surviving >100 days. This observation strongly supports the combination of antibody targeted T cells with chemotherapy as a novel approach for the therapy of CD19(+) B-cell malignancies.