Regression of bone metastases following adoptive transfer of anti-CD3-activated and IL-2-expanded tumor vaccine draining lymph node cells.
As many as 80% of patients with breast, prostate, or lung cancer develop bone metastases during the course of their illness. However, thus far, no attempts have been made to explore the potential value of adoptive immunotherapy with antigen-specific T lymphocytes specifically for the treatment of skeletal metastases. Here, we demonstrate tumor regression in a preclinical model of bone metastases from the murine B16BL6 melanoma following adoptive transfer of effector T lymphocytes obtained from tumor vaccine draining lymph nodes. The antitumor effect required transfer of high number of effector cells, which was dependent on CD8+ cells as demonstrated by in vivo depletion of different T cell subsets, and was magnified if effector cells were administered to the arterial supply of the bone/bone marrow. Using flow cytometric analysis, CFSE-labelled Thy1.1+ donor T cells were isolated from the bone marrow of tumor-bearing mice at 24 h and 6 days following adoptive transfer. At the latter time point cell division of the transferred effector cells was detectable. Currently, no curative treatment is known for skeletal metastases in clinical practice. Considering the promising early findings in the present study, further studies exploring the therapeutic potential of adoptive immunotherapy for metastatic disease to the skeleton are warranted.
Rüttinger
Dominik
D
Robert W Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon 97213, USA.
Li
Rui
R
Urba
Walter J
WJ
Fox
Bernard A
BA
Hu
Hong-Ming
HM
D000818:Animals; D001859:Bone Neoplasms / Q000556:secondary* / Q000628:therapy*; D017252:CD3 Complex / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D005260:Female; D016219:Immunotherapy, Adoptive; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*
D017252:CD3 Complex; D019496:Cancer Vaccines