Brian G Till1, Oliver W Press. 1. Research Associate, Acting Instructor, University of Washington, Fred Hutchinson Cancer Research Center, Department of Medicine, Seattle, WA 98109, USA. tillb@fhcrc.org
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.
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.
Authors: H E Heslop; M K Brenner; C Rooney; R A Krance; W M Roberts; R Rochester; C A Smith; V Turner; J Sixbey; R Moen Journal: Hum Gene Ther Date: 1994-03 Impact factor: 5.695
Authors: E B Papadopoulos; M Ladanyi; D Emanuel; S Mackinnon; F Boulad; M H Carabasi; H Castro-Malaspina; B H Childs; A P Gillio; T N Small Journal: N Engl J Med Date: 1994-04-28 Impact factor: 91.245
Authors: E A Walter; P D Greenberg; M J Gilbert; R J Finch; K S Watanabe; E D Thomas; S R Riddell Journal: N Engl J Med Date: 1995-10-19 Impact factor: 91.245