title: Bryostatin 1-activated T cells can traffic and mediate tumor regression.
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-206 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.
authors.affiliation: Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
authors.forename: T M
authors.initials: TM
authors.lastname: Tuttle
authors.forename: K P
authors.initials: KP
authors.lastname: Bethke
authors.forename: T H
authors.initials: TH
authors.lastname: Inge
authors.forename: C W
authors.initials: CW
authors.lastname: McCrady
authors.forename: G R
authors.initials: GR
authors.lastname: Pettit
authors.forename: H D
authors.initials: HD
authors.lastname: Bear
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D054713:Bryostatins; D005260:Female; D016219:Immunotherapy, Adoptive; D007783:Lactones / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008213:Lymphocyte Activation / Q000187:drug effects*; D018942:Macrolides; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1