Bispecific monoclonal antibodies directed to CD16 and to a tumor-associated antigen induce target-cell lysis by resting NK cells and by a subset of NK clones

S. Ferrini, I. Prigione, S. Miotti, E. Ciccone, C. Cantoni, Q. Chen, M. I. Colnaghi, L. Moretta

Research output: Contribution to journalArticle

Abstract

CD16 surface antigens represent activatory molecules in CD3-16+ NK cells. In order to target NK cells against relatively NK-resistant ovarian carcinomas, we usedan anti-CD16 monoclonal antibody (MAb) (VD4), together with an anti-ovarian carcinoma-associated antigen (MOV19), to construct biMAbs. To this end, hybrid hybridomas were generated by fusing a TK-deficient VD4 hybridoma mutant with a HGPRT-deficient MOV19 hybrid. Supernatants from hybrid hybridomas that had been selected in HAT medium were screened for their ability to induce a CD3-16+ NK clone to lyse an MOV19+ ovarian carcinoma cell line in a 4-hr 51Cr-release assay. The NMB.45 hybrid hybridoma secreted a biMAb which triggered lysis of MOV19+ but not of MOV19- target cells. Some degree of target cell lysis was also observed with MOV19 MAb (due to ADCC mechanisms), while the VD4 MAb was ineffective. HPLC fractionation of MAbs secreted by the hybrid hybridoma made it possible to identify 4 different peaks, one of which appeared to contain functional biMAb molecules. HPLC-purified biMAb (100 ng/ml) induced resting PBL to lyse the 'NK-resistant' IGROVI ovarian carcinoma cell line. Fresh MOV19+ tumor cells were also lysed, although with lower efficiency. When IL-2-activated lymphocytes were used as a source of effectors, biMAb caused only minor increases in the IL-2-induced cytolytic activity. Further analyses of the effect of biMAb were performed at the clonal level. Among CD3-16+ NK cell clones, a clear enhancing effect could be observed only in GL183+ but not in GL183- clones. In CD3+ cytotoxic clones a triggering effect could be detected in one out of 4 TCR γ/β+ clones but not in TCR α/β+ clones.

Original languageEnglish
Pages (from-to)227-233
Number of pages7
JournalInternational Journal of Cancer
Volume48
Issue number2
Publication statusPublished - 1991

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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