Trial Watch: Adoptive cell transfer for oncological indications

Abstract

One particular paradigm of anticancer immunotherapy relies on the administration of (potentially) tumor-reactive immune effector cells. Generally, these cells are obtained from autologous peripheral blood lymphocytes (PBLs) ex vivo (in the context of appropriate expansion, activation and targeting protocols), and re-infused into lymphodepleted patients along with immunostimulatory agents. In spite of the consistent progress achieved throughout the past two decades in this field, no adoptive cell transfer (ACT)-based immunotherapeutic regimen is currently approved by regulatory agencies for use in cancer patients. Nonetheless, the interest of oncologists in ACT-based immunotherapy continues to increase. Accumulating clinical evidence indicates indeed that specific paradigms of ACT, such as the infusion of chimeric antigen receptor (CAR)-expressing autologous T cells, are associated with elevated rates of durable responses in patients affected by various neoplasms. In line with this notion, clinical trials investigating the safety and therapeutic activity of ACT in cancer patients are being initiated at an ever increasing pace. Here, we review recent preclinical and clinical advances in the development of ACT-based immunotherapy for oncological indications.

Keywords: GM-CSF; TCR; TLR agonists; checkpoint blockers; chimeric antigen receptor; tumor-associated antigens.