Targeting of 'T' lymphocytes against human hepatoma cells by a bispecific monoclonal antibody: Role of different lymphocyte subsets

Q. Chen, P. Sun, I. Prigione, H. Xie, S. Ferrini

Research output: Contribution to journalArticle

Abstract

In an attempt to construct biphasic monoclonal antibodies (bimAbs) able to target cytotoxic T lymphocytes against human hepatoma cells, an HGPRT-deficient mutant of the Hepama-6 hybridoma, which produces an antihuman-hepatoma mAb, was directly fused with splenocytes from Balb/C mice immunized by a polyclonal cytotoxic T-cell line. Hybrid hybridomas were selected in HAT medium, and their supernatants were directly screened for the ability to induce IL-2-cultured cytotoxic T lymphocytes to kill hepatoma cells in a 51Cr-release assay. The selected hybrid hybridoma, termed DQ-33, secretes a bimAb, which reacts with a CD3-associated determinant. When resting peripheral-blood lymphocytes were used as effector cells, virtually no cytolytic activity could be induced by DQ-33, whereas phytohemagglutinin-activated lymphocytes that had been expanded in vitro in IL-2-containing medium could be efficiently targeted against hepatoma cells. Targeting by DQ-33 bimAb was analyzed on different subsets of IL-2-cultured lymphocytes. It was evident that CD+4-8+ TCRα/β+ and CD3+4-8-TCRγ/δ+ lymphocytes were efficiently induced by bimAb to lyse human hepatoma cells, whereas no induction of cytolysis could be observed when CD3+4+8-TCRα/β+ cells were used as effectors. DQ-33 bimAb was also able to induce lymphokine secretion (IL-2, GM-CSF and TNFα) by all the differet subsets of lymphocytes analyzed in the presence of target cells expressing the relevant antigen, independent of the expression of cytolytic activity.

Original languageEnglish
Pages (from-to)79-86
Number of pages8
JournalTumori
Volume78
Issue number2
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Cancer Research

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