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

Monica Rodolfo, Cinzia Bassi, Carolina Salvi, Giorgio Parmiani

Research output: Contribution to journalArticle

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 α/βTCR+Vβ6+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 histotype 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-α/βTCR and anti-Vβ6 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 tumourbearing animals and used in adoptive immunotherapy of tumours previously shown to be lysed in vitro by these effectors.

Original languageEnglish
Pages (from-to)53-62
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume34
Issue number1
DOIs
Publication statusPublished - Jan 1991

Keywords

  • Adoptive immunotherapy
  • Common tumour-associated antigens
  • Cytotoxic T cell line

ASJC Scopus subject areas

  • Oncology
  • Immunology
  • Cancer Research

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