Therapeutic use of a long-term cytotoxic T cell line recognizing a common tumour-associated antigen: the pattern of in vitro reactivity predicts the in vivo effect on different tumours

Cancer Immunol Immunother. 1991;34(1):53-62. doi: 10.1007/BF01741325.

Abstract

A long-term-cultured cytotoxic T lymphocyte (CTL) line (E/88) was obtained from splenic lymphocytes of BALB/c (H-2d) mice bearing the weakly immunogenic colonic carcinoma C26. This line was shown to be alpha/beta TCR + V beta 6 + CD3 + CD8 + CD4- and to recognize a common tumour-associated antigen on syngeneic carcinomas and sarcomas in a major-histocompatibility--complex-restricted and T-cell-receptor(TCR)-mediated fashion. The assessment of cytotoxic activity on a panel of 30 normal and neoplastic target cells of differing etiology and histo-type showed that E/88 CTL lysed syngeneic colon carcinomas and some fibrosarcomas but not leukemias, lymphomas or mammary carcinomas. Clones derived from the E/88 line exhibited the same lytic pattern. Moreover, anti-T3, anti-Lyt2.2, anti-alpha/beta TCR and anti-V beta 6 mAbs as well as anti-H-2d antisera abolished cytotoxicity when used in blocking experiments. The therapeutic activity of E/88 CTL upon in vivo transfer was assessed in mice bearing either experimental or spontaneous metastases of C26. In both models therapy with E/88 lymphocytes in combination or not with interleukin-2 was highly effective. Adoptive immunotherapy carried out with two clones obtained from line E/88 showed comparable therapeutic effects. In addition, treatment of syngeneic mice bearing experimental metastases of in vitro E/88-lysable or E/88-resistant tumours, showed that E/88 CTL can eradicate metastases of the former but not of the latter neoplasms. These data indicate that long-term CTL lines recognizing common tumour-associated antigens can be derived from tumour-bearing animals and used in adoptive immunotherapy of tumours previously shown to be lysed in vitro by these effectors.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, Neoplasm / analysis*
  • Cell Line
  • Cytotoxicity, Immunologic
  • Immunotherapy, Adoptive*
  • Interleukin-2 / pharmacology
  • Mice
  • Mice, Inbred Strains
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / therapy*
  • Phenotype
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • Interleukin-2
  • Receptors, Antigen, T-Cell