Use of anti-CD3 and anti-CD16 bispecific monoclonal antibodies for the targeting of T and NK cells against tumor cells.

S. Ferrini, A. Cambiaggi, S. Sforzini, S. Canevari, D. Mezzanzanica, M. I. Colnaghi, L. Moretta

Research output: Contribution to journalArticle

Abstract

To target T lymphocytes against EGF-R+ tumors, we constructed anti-CD3/anti-EGF-R bimAbs either by the generation of a hybrid hybridoma (quadroma) or by a chemical cross-linking method. Analysis of the in vitro functional activity of these two different constructs indicated that the quadroma-secreted bimAb was more efficient in targeting the CD3+8+ clones against EGF-R+ target cells with respect to the bimAb produced by chemical method. In addition, the quadroma-produced bimAb is able to induce cytolysis of EGF-R+ tumor cell lines of PHA-induced lymphoblasts that had been expanded in IL-2-containing medium, whereas tumor cells lacking expression of EGF-R were not lysed. Resting PBL targeted by the bimAb did not display significant cytotoxicity against the relevant tumor. An anti-CD16 hybridoma (IgG1) was fused with an anti-folate-binding protein hybrid (IgG2a) to construct bimAbs to target NK cells against NK-resistant ovarian carcinomas. The hybrid IgG1/IgG2a bimAb triggered the specific lysis of relevant target cells by resting NK cells, but it was ineffective when CD8+TCR alpha/beta+ cultured cell populations were used as effectors. Only marginal increases of cytolytic activity could be induced by the bimAb when IL-2-activated PBL (i.e., LAK cells) were used as effectors due to the high cytolytic activity of these cells against the relevant tumors in the absence of bimAb. The possible use of anti-CD16 or anti-CD3 bimAbs for the development of different cellular immunotherapy strategies against cancer is discussed.

Original languageEnglish
Pages (from-to)295-300
Number of pages6
JournalCancer Detection and Prevention
Volume17
Issue number2
Publication statusPublished - 1993

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Bispecific Antibodies
Epidermal Growth Factor
Natural Killer Cells
T-Lymphocytes
Hybridomas
Neoplasms
Interleukin-2
Immunoglobulin G
Lymphokine-Activated Killer Cells
Tumor Cell Line
Folic Acid
Immunotherapy
Cultured Cells
Carrier Proteins
Clone Cells
Carcinoma
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Use of anti-CD3 and anti-CD16 bispecific monoclonal antibodies for the targeting of T and NK cells against tumor cells. / Ferrini, S.; Cambiaggi, A.; Sforzini, S.; Canevari, S.; Mezzanzanica, D.; Colnaghi, M. I.; Moretta, L.

In: Cancer Detection and Prevention, Vol. 17, No. 2, 1993, p. 295-300.

Research output: Contribution to journalArticle

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