Bryostatin 1-activated T cells can traffic and mediate tumor regression.
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.
Tuttle
T M
TM
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Bethke
K P
KP
Inge
T H
TH
McCrady
C W
CW
Pettit
G R
GR
Bear
H D
HD
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*
D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1