Activation of mononuclear cells to be used for hybrid monoclonal antibody-induced lysis of human ovarian carcinoma cells

S. M. Pupa, S. Canevari, R. Fontanelli, S. Menard, D. Mezzanzanica, A. Lanzavecchia, M. I. Colnaghi

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Abstract

Recently we reported that cytotoxic T-cell clones can be re-targeted to unrelated tumor cells by bispecific monoclonal antibodies (MAbs), anti-CD3 and anti-ovarian carcinoma (αOC/TR) (Mezzanzanica et al., 1988). In the perspective of in vivo tumor immunotherapy, as an alternative to cytotoxic T lymphocytes (CTL) from T-cell clones, since human peripheral blood mononuclear cells (PBMCs) without stimulation were quite ineffective, a suitable in vitro activation method was developed to render PBMCs lytic for relevant targets in the presence of the bispecific hybrid MAb αOC/TR. This activation protocol was applied to PBMCs from 9 healthy donors (HD) and 6 ovarian carcinoma patients (P) and to tumor-associated lymphocytes (TAL) from 4 ovarian carcinoma P. The method consisted of in vitro stimulation with phytohemagglutinin (PHA) for 2 days, followed by culture with a low dose of recombinant human interleukin-2 (rIL-2) for 6 to 10 days. The antibody-mediated lysis of CTL from HD PBMCs was found to be specifically directed against cells expressing the relevant ovarian tumor antigen when different tumor cell lines and short-term cultures of tumor and normal cells were tested. The antibody-mediated lysis of CTL and P PBMCs or TAL was efficient both on autologous and allogeneic ovarian tumor cells, whereas no reactivity with autologous normal cells was observed and LAK activity was only evident in 1 out of 4 cases. The hybrid antibody induced cytotoxic activity of CTL from P was, however, lower than that of CTL from HD.

Original languageEnglish
Pages (from-to)455-459
Number of pages5
JournalInternational Journal of Cancer
Volume42
Issue number3
Publication statusPublished - 1988

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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