PT  - JOURNAL ARTICLE
AU  - Tuttle, Todd M.
AU  - Inge, Thomas H.
AU  - Bethke, Kevin P.
AU  - McCrady, Carl W.
AU  - Pettit, George R.
AU  - Bear, Harry D.
TI  - Activation and Growth of Murine Tumor-specific T-Cells Which Have <em>in Vivo</em> Activity with Bryostatin 1
DP  - 1992 Feb 01
TA  - Cancer Research
PG  - 548--553
VI  - 52
IP  - 3
4099  - http://cancerres.aacrjournals.org/content/52/3/548.short
4100  - http://cancerres.aacrjournals.org/content/52/3/548.full
SO  - Cancer Res1992 Feb 01; 52
AB  - We examined the ability of bryostatin 1 (Bryo), a novel protein kinase C activator, plus ionomycin (Io), a calcium ionophore, to activate T-cells with specific antitumor activity. Lymphocytes from the draining lymph nodes (DLN) of MCA-105 tumor-bearing host mice were stimulated with Bryo/Io, either fresh or after in vitro stimulation with autologous tumor, and then were incubated in interleukin-2 at 20 units/ml. Lymphocytes sensitized with tumor cells in vitro and then stimulated with Bryo/Io exhibited significant expansion (12-fold) after a total of 3 weeks in culture and moderate cytolytic activity (40% at an effector:tumor cell ratio of 80:1) and were exclusively CD8+ T-cells. DLN cells activated immediately with Bryo/Io, without tumor antigen sensitization in vitro, displayed marked growth (130-fold expansion) over 3 weeks in culture, had weak cytolytic activity (8% at an effector:tumor ratio of 80:1), and were a mixed population of CD8+ and CD4+ cells. Despite the differences in phenotypes and in cytotoxicity, both groups of DLN cells were highly effective in vivo against MCA-105 pulmonary metastases. Bryo/Io-activated DLN cells from MCA-105 tumor-bearing hosts had no therapeutic efficacy against B16 melanoma or MCA-203 sarcoma metastases. Lymph node cells from normal mice and non-draining lymph node cells from tumor-bearing hosts could be expanded with Bryo/Io to a degree similar to that of DLN cells but had no antitumor activity. Phenotypic analyses and in vitro and in vivo depletion studies demonstrate that CD8+ cells mediated tumor regression. ©1992 American Association for Cancer Research.