Bi- and Tri-Specific T Cell Engager-Armed Oncolytic Viruses: Next-Generation Cancer Immunotherapy

• Published in: Biomedicines Vol. 8; no. 7; p. 204
• Main Authors: Guo, Zong Sheng, Lotze, Michael T, Zhu, Zhi, Storkus, Walter J, Song, Xiao-Tong
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.07.2020; MDPI
• Subjects: Antibodies; Antigen (tumor-associated); Antigens; Apoptosis; bispecific antibody; bispecific T cell engager; Cancer; Cancer immunotherapy; Cancer therapies; Cell culture; Clinical outcomes; Cytokines; Cytotoxicity; Dendritic cells; FDA approval; Genes; Immunotherapy; Infections; Lymphocytes; Lymphocytes T; Oncolysis; oncolytic virus; Review; T cell receptors; trispecific antibody; trispecific T cell engager; tumor antigen-specific T cells; Tumors; Vaccines; Viral infections; Viruses; tumor antigen-specific T cells; bispecific T cell engager; oncolytic virus; trispecific T cell engager; adenovirus; bispecific antibody; trispecific antibody; vaccinia virus; measles virus
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/BIOMEDICINES8070204

Oncolytic viruses (OVs) are potent anti-cancer biologics with a bright future, having substantial evidence of efficacy in patients with cancer. Bi- and tri-specific antibodies targeting tumor antigens and capable of activating T cell receptor signaling have also shown great promise in cancer immunotherapy. In a cutting-edge strategy, investigators have incorporated the two independent anti-cancer modalities, transforming them into bi- or tri-specific T cell engager (BiTE or TriTE)-armed OVs for targeted immunotherapy. Since 2014, multiple research teams have studied this combinatorial strategy, and it showed substantial efficacy in various tumor models. Here, we first provide a brief overview of the current status of oncolytic virotherapy and the use of multi-specific antibodies for cancer immunotherapy. We then summarize progress on BiTE and TriTE antibodies as a novel class of cancer therapeutics in preclinical and clinical studies, followed by a discussion of BiTE- or TriTE-armed OVs for cancer therapy in translational models. In addition, T cell receptor mimics (TCRm) have been developed into BiTEs and are expected to greatly expand the application of BiTEs and BiTE-armed OVs for the effective targeting of intracellular tumor antigens. Future applications of such innovative combination strategies are emerging as precision cancer immunotherapies.