Developing T-cell therapies for lymphoma without receptor engineering

Abstract

T-cell therapy has emerged from the bench for the treatment of patients with lymphoma. Responses to T-cell therapeutics are regulated by multiple factors, including the patient's immune system status and disease stage. Outside of engineering of chimeric antigen receptors and artificial T-cell receptors, T-cell therapy can be mediated by ex vivo expansion of antigen-specific T cells targeting viral and/or nonviral tumor-associated antigens. These approaches are contributing to enhanced clinical responses and overall survival. In this review, we summarize the available T-cell therapeutics beyond receptor engineering for the treatment of patients with lymphoma.

Figure 1.

Antigen-specific T-cell strategies for lymphomas. (A) In vivo, intracellular antigens are presented on MHC-I molecules, where CTLs can engage directly with the MHC-I–peptide complex on the surface of the cancer cell. Surface antigens can be targeted indirectly via presentation by antigen-presenting cells or directly by antibodies. This process is often ineffective in cancer patients. (B) Antigen presentation is enhanced in T-cell–mediated therapies, as tumor-derived material is presented by appropriately activated antigen-presenting cells, most commonly DCs. Antigenic DC loading of tumor-associated viral peptides, lysed tumor cells, known antigenic tumor peptides, total tumor RNA (TTRNA), and minor histocompatibility proteins have all been attempted in hematological T-cell–based immunotherapy. (C) T-cell–based therapies enhance the T-cell response by ensuring appropriate costimulation and optimal environmental conditions for T-cell activation. This process allows TAA-specific T-cell clones, or polyclonal multiantigen-specific T cells, to be expanded ex vivo from patients or healthy donors for infusion into patients.