Bedside to bench and back again: how animal models are guiding the development of new immunotherapies for cancer.
Immunotherapy using adoptive cell transfer is a promising approach that can result in the regression of bulky, invasive cancer in some patients. However, currently available therapies remain less successful than desired. To study the mechanisms of action and possible improvements in cell-transfer therapies, we use a murine model system with analogous components to the treatment of patients. T cell receptor transgenic CD8+ T cells (pmel-1) specifically recognizing the melanocyte differentiation antigen gp100 are adoptively transferred into lympho-depleted mice bearing large, established, 14-day subcutaneous B16 melanoma (0.5-1 cm in diameter) on the day of treatment. Adoptive cell transfer in combination with interleukin interleukin-2 or interleukin-15 cytokine administration and vaccination using an altered form of the target antigen, gp100, can result in the complete and durable regression of large tumor burdens. Complete responders frequently develop autoimmunity with vitiligo at the former tumor site that often spreads to involve the whole coat. These findings have important implications for the design of immunotherapy trials in humans.
Finkelstein
Steven E
SE
National Cancer Institute, National Institutes of Health, Building 10, Room 2B-46, 10 Center Drive, Bethesda, MD 20892, USA. Steven_Finkelstein@nih.gov
Heimann
David M
DM
Klebanoff
Christopher A
CA
Antony
Paul A
PA
Gattinoni
Luca
L
Hinrichs
Christian S
CS
Hwang
Leroy N
LN
Palmer
Douglas C
DC
Spiess
Paul J
PJ
Surman
Deborah R
DR
Wrzesiniski
Claudia
C
Yu
Zhiya
Z
Rosenberg
Steven A
SA
Restifo
Nicholas P
NP
D019264:Adoptive Transfer; D000818:Animals; D004195:Disease Models, Animal; D007167:Immunotherapy; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D009362:Neoplasm Metastasis / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology