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Antibodies 2018, 7(1), 3; https://doi.org/10.3390/antib7010003

Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity

Novimmune S.A., 14 chemin des Aulx, CH-1228 Geneva, Switzerland
Present address: EPFL SV ISREC UPORICCHIO, SV 2824, CH-1015 Lausanne, Switzerland.
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Author to whom correspondence should be addressed.
Received: 30 October 2017 / Revised: 22 December 2017 / Accepted: 22 December 2017 / Published: 3 January 2018
(This article belongs to the Special Issue Monoclonal Antibodies)
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Abstract

CD47 serves as an anti-phagocytic receptor that is upregulated by cancer to promote immune escape. As such, CD47 is the focus of intense immuno-oncology drug development efforts. However, as CD47 is expressed ubiquitously, clinical development of conventional drugs, e.g., monoclonal antibodies, is confronted with patient safety issues and poor pharmacology due to the widespread CD47 “antigen sink”. A potential solution is tumor-directed blockade of CD47, which can be achieved with bispecific antibodies (biAbs). Using mouse CD47-blocking biAbs in a syngeneic tumor model allowed us to evaluate the efficacy of tumor-directed blockade of CD47 in the presence of the CD47 antigen sink and a functional adaptive immune system. We show here that CD47-targeting biAbs inhibited tumor growth in vivo, promoting durable antitumor responses and stimulating CD8+ T cell activation in vitro. In vivo efficacy of the biAbs could be further enhanced when combined with chemotherapy or PD-1/PD-L1 immune checkpoint blockade. We also show that selectivity and pharmacological properties of the biAb are dependent on the affinity of the anti-CD47 arm. Taken together, our study validates the approach to use CD47-blocking biAbs either as a monotherapy or part of a multi-drug approach to enhance antitumor immunity. View Full-Text
Keywords: bispecific antibodies; CD47; antitumor immunity; immunotherapy; immunosurveillance; checkpoint inhibitors; phagocytosis bispecific antibodies; CD47; antitumor immunity; immunotherapy; immunosurveillance; checkpoint inhibitors; phagocytosis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Dheilly, E.; Majocchi, S.; Moine, V.; Didelot, G.; Broyer, L.; Calloud, S.; Malinge, P.; Chatel, L.; Ferlin, W.G.; Kosco-Vilbois, M.H.; Fischer, N.; Masternak, K. Tumor-Directed Blockade of CD47 with Bispecific Antibodies Induces Adaptive Antitumor Immunity. Antibodies 2018, 7, 3.

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