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Open AccessFeature PaperReview

Discovery Strategies to Maximize the Clinical Potential of T-Cell Engaging Antibodies for the Treatment of Solid Tumors

1
Biotherapeutics Discovery, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA
2
Cancer Immunology & Immune Modulation, Boehringer Ingelheim RCV GmbH & Co KG, Dr. Boehringer-Gasse 5-11, 1121 Vienna, Austria
*
Author to whom correspondence should be addressed.
Antibodies 2020, 9(4), 65; https://doi.org/10.3390/antib9040065
Received: 13 September 2020 / Revised: 21 October 2020 / Accepted: 11 November 2020 / Published: 18 November 2020
(This article belongs to the Special Issue Monoclonal Antibody-Directed Therapy)
T-cell Engaging bispecific antibodies (TcEs) that can re-direct cytotoxic T-cells to kill cancer cells have been validated in clinical studies. To date, the clinical success with these agents has mainly been seen in hematologic tumor indications. However, an increasing number of TcEs are currently being developed to exploit the potent mode-of-action to treat solid tumor indications, which is more challenging in terms of tumor-cell accessibility and the complexity of the tumor microenvironment (TME). Of particular interest is the potential of TcEs as an immunotherapeutic approach for the treatment of non-immunogenic (often referred to as cold) tumors that do not respond to checkpoint inhibitors such as programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) antibodies. This has led to considerable discovery efforts for, firstly, the identification of tumor selective targeting approaches that can safely re-direct cytotoxic T-cells to cancer cells, and, secondly, bispecific antibodies and their derivatives with drug-like properties that promote a potent cytolytic synapse between T-cells and tumor cells, and in the most advanced TcEs, have IgG-like pharmacokinetics for dosing convenience. Based on encouraging pre-clinical data, a growing number of TcEs against a broad range of targets, and using an array of different molecular structures have entered clinical studies for solid tumor indications, and the first clinical data is beginning to emerge. This review outlines the different approaches that have been taken to date in addressing the challenges of exploiting the TcE mode-of-action for a broad range of solid indications, as well as opportunities for future discovery potential. View Full-Text
Keywords: T-cell engagers; bispecific antibodies; immunotherapy; oncology; antibody engineering; immunological synapse T-cell engagers; bispecific antibodies; immunotherapy; oncology; antibody engineering; immunological synapse
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MDPI and ACS Style

Voynov, V.; Adam, P.J.; Nixon, A.E.; Scheer, J.M. Discovery Strategies to Maximize the Clinical Potential of T-Cell Engaging Antibodies for the Treatment of Solid Tumors. Antibodies 2020, 9, 65.

AMA Style

Voynov V, Adam PJ, Nixon AE, Scheer JM. Discovery Strategies to Maximize the Clinical Potential of T-Cell Engaging Antibodies for the Treatment of Solid Tumors. Antibodies. 2020; 9(4):65.

Chicago/Turabian Style

Voynov, Vladimir; Adam, Paul J.; Nixon, Andrew E.; Scheer, Justin M. 2020. "Discovery Strategies to Maximize the Clinical Potential of T-Cell Engaging Antibodies for the Treatment of Solid Tumors" Antibodies 9, no. 4: 65.

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