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

T. M. Tuttle, T. H. Inge, D. S. Lind, H. D. Bear

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)299-307
Number of pages9
JournalSurgical Oncology
Volume1
Issue number4
DOIs
StatePublished - Aug 1992
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grant CA48075 from DHHS, NCI. THI is a recipient of a Medical Scholars Award from the AD. Williams Foundation and a scholarship award from the Norfolk Foundation.

Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.

Keywords

  • adoptive immunotherapy
  • bryostatin 1
  • effector cells
  • protein kinase C

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