Education and Empowering Special Forces to Eradicate Secret Defectors: Immune System-Based Treatment Approaches for Mature T- and NK-Cell Malignancies

Abstract

Mature T- and NK-cell leukemia/lymphoma (MTCL/L) constitute a heterogeneous group of, currently, 30 distinct neoplastic entities that are overall rare, and all present with a challenging molecular markup. Thus, so far, the use of first-line cancer treatment modalities, including chemotherapies, achieve only limited clinical responses associated with discouraging prognoses. Recently, cancer immunotherapy has evolved rapidly, allowing us to help patients with, e.g., solid tumors and also relapsed/refractory B-cell malignancies to achieve durable clinical responses. In this review, we systematically unveiled the distinct immunotherapeutic approaches available, emphasizing the special impediments faced when trying to employ immune system defense mechanisms to target ‘one of their own—gone mad’. We summarized the preclinical and clinical efforts made to employ the various platforms of cancer immunotherapies including antibody-drug conjugates, monoclonal as well as bispecific antibodies, immune-checkpoint blockades, and CAR T cell therapies. We emphasized the challenges to, but also the goals of, what needs to be done to achieve similar successes as seen for B-cell entities.

Broadening the horizon: potential applications of CAR-T cells beyond current indications

“…A T-cell depleting therapy would lead to a complete eradication of T cells, resulting in detrimental infectious complications ( 27 ). The second fundamental challenge in employing CAR-T-cell therapy for T-cell malignancies is the apheresis of exclusively healthy T cells from the patient in order to generate CAR-T cells without contamination with circulating tumor cells ( 28 ).…”