Targeting of T or NK lymphocytes against tumor cells by bispecific monoclonal antibodies

Role of different triggering molecules

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

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

MAbs directed against triggering surface molecules expressed by T lymphocytes (CD3, TCR, CD2, CD28) or by NK cells (CD2, CD16) are able to induce the functional program of these cells. These MAbs represent suitable reagents to construct biMAbs directed against TAA, in order to specifically target effector lymphocytes against tumor cells. Anti-CD3/anti-EGF-R biMAbs were constructed to specifically direct T lymphocytes against EGF-R+ tumor cells. Such biMAb are able to induce cytolysis of EGF-R+ tumor cell lines (A431, IGROV, KATO-III and U-87) by cytolytic CD3+ effector lymphocytes while tumor cells having low or absent expression of EGF-R were not lysed. In addition, both cytolytic T (CD8+) cells and non-cytolytic (CD4+) IL-2-expanded lymphocytes were able to secrete lymphokines upon contact with EGF-R+ tumor cells. To target NK cells against NK resistant ovarian carcinomas, we used an anti-CD16 MAb (IgG1) together with an anti-ovarian carcinoma MAb (IgG(2a)), to construct biMAbs using the hybrid hybridoma technique. The hybrid IgG1/IgG(2a) biMAb triggered the specific lysis of relevant target cells by resting NK cells and by a subset of NK clones. In addition, some TCR γ/δ+ clones but not TCR α/β+ clones could be targeted by the biMAb.

Original languageEnglish
Pages (from-to)15-18
Number of pages4
JournalInternational Journal of Cancer
Issue numberSUPPL. 7
Publication statusPublished - 1992

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Bispecific Antibodies
Lymphocytes
Epidermal Growth Factor
Immunoglobulin G
Neoplasms
Natural Killer Cells
Clone Cells
Carcinoma
T-Lymphocytes
Lymphokines
Hybridomas
Tumor Cell Line
Interleukin-2

ASJC Scopus subject areas

  • Cancer Research
  • Medicine(all)
  • Oncology

Cite this

Targeting of T or NK lymphocytes against tumor cells by bispecific monoclonal antibodies : Role of different triggering molecules. / Ferrini, S.; Cambiaggi, A.; Cantoni, C.; Canevari, S.; Mezzanzanica, D.; Colnaghi, M. I.; Moretta, L.

In: International Journal of Cancer, No. SUPPL. 7, 1992, p. 15-18.

Research output: Contribution to journalArticle

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AU - Ferrini, S.

AU - Cambiaggi, A.

AU - Cantoni, C.

AU - Canevari, S.

AU - Mezzanzanica, D.

AU - Colnaghi, M. I.

AU - Moretta, L.

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