Regression of established
tumors can be induced by adoptive immunotherapy (AIT) with
tumor draining lymph node (DLN) lymphocytes activated with
bryostatin and
ionomycin (B/I).
Tumor antigen-sensitized DLN lymphocytes from BALB/c mice with 10-day 4T1 mammary
carcinomas were harvested, activated with B/I, and expanded in culture with either
interleukin-2 (IL-2) or
IL-7 +
IL-15. Cell yields, proliferation, phenotypes, and in vitro responses to
tumor antigen were compared for cells grown in different
cytokines. These T cells were also tested for antitumor activity against established 4T1 mammary
carcinomas after inoculation of
tumor cells subcutaneously (s.c.). IL-7/15 resulted in much faster and more prolonged proliferation of B/I-activated T cells than culturing the same cells in
IL-2. This resulted in approximately 5-10-fold greater yields of viable cells. Culture in IL-7/15 yielded higher proportions of CD8(+) T cells and a higher proportion of cells with a central memory phenotype. T cells grown in
IL-2 had higher
interferon-gamma (IFN-gamma) release responses to
tumor antigen than cells grown in IL-7/15. Adoptive transfer of B/I-activated T cells grown in IL-7/15 demonstrated much greater efficacy against 4T1
tumors in vivo. Activation of
tumor antigen-sensitized T cells with B/I and culture in
IL-7 +
IL-15 is a promising modification of standard regimens for production of T cells for use in AIT of
cancer.