Bryostatin 1-activated T cells can traffic and mediate tumor regression

Todd M. Tuttle, Kevin P. Bethke, Thomas H. Inge, Carl W. McCrady, George Pettit, Harry D. Bear

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Adoptive immunotherapy in humans may be limited by the lack of autologous tumor cells to activate and expand tumor-specific T cells. Pharmacologic manipulation of protein kinase C (PKC) and intracellular calcium may substitute for tumor antigen and stimulate T cells for adoptive immunotherapy. In the present study, we evaluated the ability of the PKC activator Bryostatin 1 (B) plus the calcium ionophore ionomycin (I) to activate lymphocytes obtained from popliteal lymph nodes (DLN) draining an MCA-105 footpad tumor. The adoptive transfer of B/I-stimulated DLN cells eradicated MCA-105 pulmonary metastases. These lymphocytes do not require concomitant IL-2 administration to mediate regression of lung metastases. Three days after intrasplenic injection of tumor cells and splenectomy, mice were given iv injections of B/I-stimulated DLN cells. Adoptive immunotherapy with these cells induced regression of established liver metastases. In an intradermal tumor model, the adoptive transfer of B/I-stimulated MCA-105 DLN cells cured mice of MCA-105 intradermal (id) tumors, but did not induce regression of MCA-203 tumors. Mice cured of MCA-105 id tumors were protected against MCA-105, but not MCA-203, tumor challenge in the footpad 7 weeks after adoptive immunotherapy.

Original languageEnglish (US)
Pages (from-to)543-548
Number of pages6
JournalJournal of Surgical Research
Volume52
Issue number6
DOIs
StatePublished - 1992

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T-Lymphocytes
Adoptive Immunotherapy
Neoplasms
Adoptive Transfer
Neoplasm Metastasis
Protein Kinase C
Lymphocytes
bryostatin 1
Lung
Injections
Ionomycin
Calcium Ionophores
Neoplasm Antigens
Splenectomy
Interleukin-2
Lymph Nodes
Calcium
Liver

ASJC Scopus subject areas

  • Surgery

Cite this

Bryostatin 1-activated T cells can traffic and mediate tumor regression. / Tuttle, Todd M.; Bethke, Kevin P.; Inge, Thomas H.; McCrady, Carl W.; Pettit, George; Bear, Harry D.

In: Journal of Surgical Research, Vol. 52, No. 6, 1992, p. 543-548.

Research output: Contribution to journalArticle

Tuttle, Todd M. ; Bethke, Kevin P. ; Inge, Thomas H. ; McCrady, Carl W. ; Pettit, George ; Bear, Harry D. / Bryostatin 1-activated T cells can traffic and mediate tumor regression. In: Journal of Surgical Research. 1992 ; Vol. 52, No. 6. pp. 543-548.
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