Treatment of lymphoma with adoptively transferred T cells

Abstract

Background: Chemotherapy-resistant lymphomas can be cured with allogeneic hematopoietic cell transplantation, demonstrating the susceptibility of these tumors to T cell mediated immune responses. However, high rates of transplant-related morbidity and mortality limit this approach. Efforts have, therefore, been made to develop alternative T cell based therapies, and there is growing evidence that adoptive therapy with T cells targeted to lymphoma-associated antigens may be a safe and effective new method for treating this group of diseases. Objective/methods: We review publications on adoptive therapy with ex vivo expanded T cells targeting viral antigens, as well as genetically modified autologous T cells, as strategies for the treatment of lymphoma, with the goal of providing an overview of these approaches. Results/conclusions: Epstein-Barr virus specific T cell therapy is an effective and safe method of treating Epstein-Barr virus associated lymphomas; however, most lymphoma subtypes do not express EBV antigens. For these diseases, adoptive immunotherapy with genetically modified T cells expressing chimeric T cell receptors targeting lymphoma-associated antigens such as CD19 and CD20 appears to be a promising alternative. Recent innovations including enhanced co-stimulation, exogenous cytokine administration and use of memory T cells promise to overcome many of the limitations and pitfalls initially encountered with this approach.