Bryostatin 1 activates T cells that have antitumor activity

Todd M. Tuttle, Thomas H. Inge, C. Paige Wirt, James L. Frank, Carl M. McCrady, Harry D. Bear

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Several strategies have been used to stimulate the growth of tumorspecific T cells in place of tumor antigen. One approach is to use pharmacologic agents to activate the second messenger pathways of T-cell activation. In the present study, we examined the ability of the protein kinase C activator bryostatin 1 (B) plus the calcium ionophore ionomycin (I) to stimulate the growth of lymphocytes obtained from the axillary lymph nodes (DLN) draining a progressively growing intradermal plasmacytoma tumor. Draining lymph node cells were initially cultured with autologous tumor cells and 20 U /ml of interleukin-2 (IL-2) for 7 days. The lymphocytes were then incubated with various concentrations of bryostatin 1 plus 1 μ,M ionomycin and cultured for an additional 14 days in IL-2. DLN cells initially cultured with autologous tumor and then restimulated with 5 nM bryostatin 1 and 1 μM ionomycin exhibited marked in vitro proliferation and 15-fold expansion of cell numbers over 2 weeks. The cells expanded with B/I were predominately CD8+ T cells and retained specific in vitro cytotoxicity against autologous tumor. When adoptively transferred to mice with established liver metastases, DLN cells restimulated with B/I-mediated specific tumor regression.

Original languageEnglish (US)
Pages (from-to)75-81
Number of pages7
JournalJournal of Immunotherapy
Volume12
Issue number2
DOIs
StatePublished - Aug 1992

Keywords

  • Adoptive immunotherapy
  • Bryostatin 1
  • Cytotoxic T-lymphocytes
  • T-cell activation

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