title: Immunotherapy of cancer: from monoclonal to oligoclonal cocktails of anti-cancer antibodies: IUPHAR Review 18.
abstract: Antibody-based therapy of cancer employs monoclonal antibodies (mAbs) specific to soluble ligands, membrane antigens of T-lymphocytes or proteins located at the surface of cancer cells. The latter mAbs are often combined with cytotoxic regimens, because they block survival of residual fractions of tumours that evade therapy-induced cell death. Antibodies, along with kinase inhibitors, have become in the last decade the mainstay of oncological pharmacology. However, partial and transient responses, as well as emergence of tumour resistance, currently limit clinical application of mAbs. To overcome these hurdles, oligoclonal antibody mixtures are being tested in animal models and in clinical trials. The first homo-combination of two mAbs, each engaging a distinct site of HER2, an oncogenic receptor tyrosine kinase (RTK), has been approved for treatment of breast cancer. Likewise, a hetero-combination of antibodies to two distinct T-cell antigens, PD1 and CTLA4, has been approved for treatment of melanoma. In a similar vein, additive or synergistic anti-tumour effects observed in animal models have prompted clinical testing of hetero-combinations of antibodies simultaneously engaging distinct RTKs. We discuss the promise of antibody cocktails reminiscent of currently used mixtures of chemotherapeutics and highlight mechanisms potentially underlying their enhanced clinical efficacy.
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Silvia
authors.initials: S
authors.lastname: Carvalho
authors.affiliation: Pharmacology and Experimental Therapeutics Unit, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Francesca
authors.initials: F
authors.lastname: Levi-Schaffer
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Michael
authors.initials: M
authors.lastname: Sela
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Yosef
authors.initials: Y
authors.lastname: Yarden
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D043025:Oligoclonal Bands / Q000276:immunology* / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D043025:Oligoclonal Bands
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