Enhancing effect of interleukin 1 alpha administration on antitumor effector T-cell development.
Antitumor effector T cells can be generated from tumor-draining lymph node cells by activation with anti-CD3 monoclonal antibody and interleukin 2. Fresh tumor-draining lymph node cells do not have antitumor activity, but after anti-CD3 monoclonal antibody-interleukin 2 activation, these cells mediate immunologically specific tumor regression in vivo. We examined the effect of interleukin 1 alpha administration on the development of effector T cells derived from tumor-draining lymph nodes. Mice were inoculated with tumor cells, and interleukin 1 alpha (180 to 720 ng) was administered on days 0, 2, and 4. Tumor-draining lymph nodes harvested 10 to 14 days later were activated in anti-CD3 monoclonal antibody for 2 days followed by expansion in interleukin 2 for 3 days. Antitumor efficacy of the activated cells was assessed in the adoptive immunotherapy of lung micrometastases. Administration of interleukin 1 alpha enhanced the antitumor reactivity of effector cells derived from tumor-draining lymph nodes without changing the immunologic specificity of the cells. Administration of interleukin 1 alpha did not alter the phenotype of fresh or activated tumor-draining lymph node cells. Interleukin 1 alpha deserves further investigation as an immune adjuvant in adoptive immunotherapy.
Sondak
V K
VK
Department of Surgery, University of Michigan Medical Center, Ann Arbor.
Tuck
M K
MK
Shu
S
S
Yoshizawa
H
H
Chang
A E
AE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D016219:Immunotherapy, Adoptive; D007375:Interleukin-1 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000628:therapy; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007375:Interleukin-1