Enhancing the Anti-Tumor Activity of Breast Cancer-Specific Cytotoxic T Lymphocytes

摘要

Directing the immune system to attack tumors represents a potential powerful approach to treat breast cancer. Our goals were to engineer the interleukin-2-receptor (IL-2R) in cytotoxic T cells (CTL) to control signal transduction through this receptor and to improve the in vivo efficacy of adoptive CTL immunotherapy. Although we produced a large number of chimeric IL- 2R, we were unsuccessful to induce T cells activation through these chimeric molecules upon transfection into T cells. However, we establish a sensitive animal tumor model system to study the interaction of a solid tumor with naive, effector and memory tumor-specific CTL. These studies indicate that naive T cells are ignorant of the tumor, but upon immunization of tumor-bearing mice with tumor-antigen peptide pulsed antigen presenting cells, the naive T cells were activated and mediated anti-tumor immune responses independent of CD4+ T helper cells. Similarly, adoptive transfer of CTL also inhibited tumor growth. Tumor-specific CTL memory T cells persisted in vivo for a long period after adoptive transfer in vivo provided the CTL were generated in vitro with IL-2. These memory CTL efficiently inhibited tumor growth suggesting that successful adoptive tumor therapy may depend on culture conditions that favor generation of memory CTL.