Genetic modification of T cell clones to improve the safety and efficacy of adoptive T cell therapy.
Our laboratory has developed methods to isolate human antigen-specific cytolytic CD8+ T cell clones and to expand such clones in vitro to numbers sufficient for T cell therapy of human diseases. Studies in immunocompromised bone marrow transplant patients at high risk for disease associated with cytomegalovirus have demonstrated that administration of more than 10(9) CD8+ T cell clones is safe and can effectively reconstitute a deficient human immune response. Our laboratory is applying this strategy of adoptive therapy to the treatment of human cancer, starting with the subset of patients with Hodgkin's disease who show expression of proteins encoded by the Epstein-Barr virus in their malignant Reed-Sternberg cells. The development of efficient systems such as retroviral vectors for the introduction of genes into primary cells has made it possible to consider overcoming some of the limitations of the effector T cells that normally mediate response to an antigen. Our laboratory is attempting to modify T cell clones by the introduction of genes before transfer as a means to improve the safety and/or efficacy of T cell therapy.
Greenberg
P D
PD
Department of Medicine, University of Washington, Seattle 98195, USA.
Nelson
B
B
Gilbert
M
M
Sing
A
A
Yee
C
C
Jensen
M
M
Riddell
S R
SR
D000956:Antigens, Viral / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002999:Clone Cells; D003586:Cytomegalovirus Infections / Q000517:prevention & control / Q000628:therapy*; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000009:adverse effects*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D000956:Antigens, Viral