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Review
. 2015 Mar 2;4(4):e1008814.
doi: 10.1080/2162402X.2015.1008814. eCollection 2015 Apr.

Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications

Aitziber Buqué  1 , Norma Bloy  2 , Fernando Aranda  3 , Francesca Castoldi  4 , Alexander Eggermont  5 , Isabelle Cremer  6 , Wolf Hervé Fridman  7 , Jitka Fucikova  8 , Jérôme Galon  9 , Aurélien Marabelle  10 , Radek Spisek  11 , Eric Tartour  12 , Laurence Zitvogel  10 , Guido Kroemer  13 , Lorenzo Galluzzi  14
Affiliations
Review

Trial Watch: Immunomodulatory monoclonal antibodies for oncological indications

Aitziber Buqué et al. Oncoimmunology. .

Abstract

Immunomodulatory monoclonal antibodies (mAbs) differ from their tumor-targeting counterparts because they exert therapeutic effects by directly interacting with soluble or (most often) cellular components of the immune system. Besides holding promise for the treatment of autoimmune and inflammatory disorders, immunomodulatory mAbs have recently been shown to constitute a potent therapeutic weapon against neoplastic conditions. One class of immunomodulatory mAbs operates by inhibiting safeguard systems that are frequently harnessed by cancer cells to establish immunological tolerance, the so-called "immune checkpoints." No less than 3 checkpoint-blocking mAbs have been approved worldwide for use in oncological indications, 2 of which during the past 12 months. These molecules not only mediate single-agent clinical activity in patients affected by specific neoplasms, but also significantly boost the efficacy of several anticancer chemo-, radio- or immunotherapies. Here, we summarize recent advances in the development of checkpoint-blocking mAbs, as well as of immunomodulatory mAbs with distinct mechanisms of action.

Keywords: CRC, colorectal carcinoma; CTLA4, cytotoxic T lymphocyte-associated protein 4; FDA, Food and Drug Administration; IL, interleukin; KIR, killer cell immunoglobulin-like receptor; MEDI4736; MPDL3280A; NK, natural killer; NSCLC, non-small cell lung carcinoma; PD-1, programmed cell death 1; RCC, renal cell carcinoma; TGFβ1, transforming growth factor β1; TLR, Toll-like receptor; TNFRSF, tumor necrosis factor receptor superfamily; Treg, regulatory T cell; ipilimumab; mAb, monoclonal antibody; nivolumab; pembrolizumab; urelumab.

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