title: Bispecific antibodies and CARs: generalized immunotherapeutics harnessing T cell redirection.
abstract: To realize the full potential of cancer immunotherapy, the latest generation immunotherapeutics are designed to harness the potent tumor-killing capacity of T cells. Thus, to mobilize T cells, new optimized bispecific antibody (BsAb) designs, enabling efficient polyclonal redirection of cytotoxic activity through binding to CD3 and a Tumor Associated Antigen (TAA) and refined genetically modified T cells have recently expanded the arsenal of available options for cancer treatment. This review presents the current understanding of the parameters crucial to the design of optimal T cell redirecting BsAb and chimeric antigen receptor (CAR)-modified T cells. However, there are additional questions that require thorough elucidation. Both modalities will benefit from design changes that may increase the therapeutic window. One such approach could employ the discrimination afforded by multiple TAA to significantly increase selectivity.
authors.affiliation: Biomunex Pharmaceuticals, 75116 Paris, France. Electronic address: ezhukovsky@biomunex.com.
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Zhukovsky
authors.affiliation: Morse Consulting, 75016 Paris, France.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Morse
authors.affiliation: Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02129, United States. Electronic address: mvmaus@mgh.harvard.edu.
authors.forename: Marcela V
authors.initials: MV
authors.lastname: Maus
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015316:Genetic Therapy; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology* / Q000637:transplantation
chemical_list: D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D019496:Cancer Vaccines; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins