Chimeric antigen receptor T cells (CAR-T) for the treatment of T-cell malignancies

Abstract

At present, the only curative therapy for patients with T-cell malignancies is allogeneic stem cell transplant, which has associated risks and toxicities. Novel agents have been tried in relapsed T-cell acute lymphoblastic leukemia (T-ALL), but only one, with 20%-30% complete remission rates, has been approved by the US Food and Drug Administration. T-ALL is a heterogeneous disease, but it has universal overexpression of CD7 as well as several other T-cell markers, such as CD2 and CD5. T cells engineered to express a chimeric antigen receptor (CAR) are a promising cancer immunotherapy. Such targeted therapies have shown great potential for inducing both remissions and even long-term relapse-free survival in patients with B-cell leukemia and lymphoma. UCART7 for CD7⁺ T-cell malignancies is in development for treatment of relapsed T-ALL in children and adults. It may also have potential in other CD7⁺ hematologic malignancies that lack both effective therapies and targeted therapies. The challenges encountered and progress made in developing a novel fratricide-resistant "off-the-shelf" CAR-T (or UCART7) that targets CD7⁺ T-cell malignancies are discussed here.

Keywords: CAR; CAR-T; Chimeric antigen receptor; Fratricide resistant; Off-the-shelf; T-ALL; T-cell acute lymphoblastic leukemia; UCART7.