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Immunotherapy of cancer: from monoclonal to oligoclonal cocktails of anti‐cancer antibodies: IUPHAR Review 18
Author(s) -
Carvalho Silvia,
LeviSchaffer Francesca,
Sela Michael,
Yarden Yosef
Publication year - 2016
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13450
Subject(s) - monoclonal antibody , medicine , cancer , antibody , antigen , immunotherapy , melanoma , cancer research , cancer immunotherapy , immunology , breast cancer , cytotoxic t cell , biology , in vitro , biochemistry
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.