Enhancing effect of interleukin 1 alpha administration on antitumor effector T-cell development

V. K. Sondak, M. K. Tuck, S. Shu, H. Yoshizawa and A. E. Chang
Department of Surgery, University of Michigan Medical Center, Ann Arbor.

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.