Adoptive transfer of bryostatin 1-activated T cells provides long-term protection from tumour metastases.
Treatment of human cancer with tumour-specific T lymphocytes is limited by the frequent unavailability of autologous tumour to stimulate T-cell growth and by the toxicity associated with high-dose interleukin-2 (IL-2) treatment. In the present study we demonstrate that Bryostatin 1 (B) plus ionomycin (I) can substitute for tumour antigen and activate tumour-bearing hosts' T-cells which provide long-term protection against tumour challenge after adoptive transfer. Lymphocytes obtained from the popliteal lymph nodes (DLN) draining an MCA-105 footpad sarcoma were stimulated with B/I, and then cultured for 7 days with 20 U ml-1 IL-2. This in vitro stimulation protocol consistently expanded cell numbers greater than 20-fold during 7 days. Mice given B/I-stimulated draining lymph node (DLN) cells were protected from specific i.v. tumour challenge for at least 15 weeks after adoptive transfer, even in the absence of IL-2 treatment. Tumour immunity conferred by B/I-activated DLN cells was systemic and independent of host T-cells. However, resistance to tumour challenge was lost when either CD4+ or CD8+ T-cells were depleted in vivo. These studies indicate that DLN cells activated with bryostatin 1 and ionomycin persist long-term in vivo as functional memory cells after adoptive transfer.
Tuttle
T M
TM
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Inge
T H
TH
Lind
D S
DS
Bear
H D
HD
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D054713:Bryostatins; D005069:Evaluation Studies as Topic; D005260:Female; D016219:Immunotherapy, Adoptive / Q000379:methods*; D015759:Ionomycin / Q000627:therapeutic use; D007783:Lactones / Q000627:therapeutic use*; D008213:Lymphocyte Activation / Q000187:drug effects*; D018942:Macrolides; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012513:Sarcoma, Experimental / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D054713:Bryostatins; D007783:Lactones; D018942:Macrolides; C046785:bryostatin 1; D015759:Ionomycin