Adoptive transfer of bryostatin 1-activated T cells provides long-term protection from tumour metastases

Surg Oncol. 1992 Aug;1(4):299-307. doi: 10.1016/0960-7404(92)90091-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Bryostatins
  • Evaluation Studies as Topic
  • Female
  • Immunotherapy, Adoptive / methods*
  • Ionomycin / therapeutic use
  • Lactones / therapeutic use*
  • Lymphocyte Activation / drug effects*
  • Macrolides
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Sarcoma, Experimental / immunology
  • Sarcoma, Experimental / therapy*
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Time Factors

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • Bryostatins
  • Lactones
  • Macrolides
  • bryostatin 1
  • Ionomycin