1. Academic Validation
  2. Research and Clinical Landscape of Bispecific Antibodies for the Treatment of Solid Malignancies

Research and Clinical Landscape of Bispecific Antibodies for the Treatment of Solid Malignancies

  • Pharmaceuticals (Basel). 2021 Aug 31;14(9):884. doi: 10.3390/ph14090884.
Gabriele Antonarelli 1 2 Federica Giugliano 1 2 Chiara Corti 1 2 Matteo Repetto 1 2 Paolo Tarantino 1 2 Giuseppe Curigliano 1 2
Affiliations

Affiliations

  • 1 Division of Early Drug Development for Innovative Therapy, European Institute of Oncology, IRCCS, 20141 Milan, Italy.
  • 2 Department of Oncology and Haematology (DIPO), University of Milan, 20122 Milan, Italy.
Abstract

Solid tumors adopt multiple mechanisms to grow, evade immune responses, and to withstand therapeutic approaches. A major breakthrough in the armamentarium of anti-cancer agents has been the introduction of monoclonal Antibodies (mAbs), able to inhibit aberrantly activated pathways and/or to unleash antigen (Ag)-specific immune responses. Nonetheless, mAb-mediated targeted pressure often fails due to escape mechanisms, mainly Ag loss/downregulation, ultimately providing therapy resistance. Hence, in order to target multiple Ag at the same time, and to facilitate cancer-immune cells interactions, bispecific Antibodies (bsAbs) have been developed and are being tested in clinical trials, yielding variable safety/efficacy results based on target selection and their structure. While in hematologic cancers the bsAb blinatumomab recently reached the Food and Drug Administration (FDA)-approval for B Cell Acute Lymphoblastic Leukemia, bsAbs use in solid tumors faces considerable challenges, such as target Ag selection, biodistribution, and the presence of an immune-suppressive tumor microenvironment (TME). This review will focus on the state-of-the art, the design, and the exploitation of bsAbs against solid malignancies, delineating their mechanisms of action, major pitfalls, and future directions.

Keywords

antibodies; bispecific; immunotherapy; solid; tumors.

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