Bispecific Antibodies, Immune Checkpoint Inhibitors, and Antibody−Drug Conjugates Directing Antitumor Immune Responses: Challenges and Prospects

• Published in: Cell biochemistry and function Vol. 42; no. 8; pp. e70011 - n/a
• Main Authors: Li, Chen Lu, Ma, Xin Yuan, Yi, Ping
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.12.2024
• Subjects: Antibodies; Antibodies, Bispecific - immunology; Antibodies, Bispecific - pharmacology; Antibodies, Bispecific - therapeutic use; antibody−drug conjugates; Anticancer properties; Antigen (tumor-associated); Antitumor activity; Bispecific antibodies; Cancer; Cancer immunotherapy; Conjugates; Conjugation; CTLA-4 protein; Drug development; Effectiveness; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - pharmacology; Immune Checkpoint Inhibitors - therapeutic use; Immune response; Immunoconjugates - pharmacology; Immunoconjugates - therapeutic use; Immunosuppressive agents; Immunotherapy; In vivo methods and tests; Inhibitors; Monoclonal antibodies; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - therapy; PD-L1 protein; Pembrolizumab; Side effects; Solid tumors; tumor heterogeneity; antibody−drug conjugates; immune checkpoint inhibitors; bispecific antibodies; monoclonal antibodies; tumor heterogeneity
• ISSN: 0263-6484; 1099-0844; 1099-0844
• DOI: 10.1002/cbf.70011

ABSTRACT Tumor immunotherapy includes bispecific antibodies (BsAbs), immune checkpoint inhibitors (ICIs), vaccines, and adoptive cell immunotherapy. BsAbs belong to the family of antibodies that can specifically target two or more different antigens and are a promising option for tumor immunotherapy. Immune checkpoints are antibodies targeting PD‐1, PD‐L1, and CTLA4 and have demonstrated remarkable therapeutic efficacy in the treatment of hematological and solid tumors, whose combination therapies have been shown to synergistically enhance the antitumor effects of BsAbs. In addition, the clinical efficacy of existing monoclonal antibodies targeting PD‐1 (e.g., ipilimumab, nivolumab, pembrolizumab, and cemiplimab) and PD‐L1 (e.g., atezolizumab, avelumab, and durvalumab) could also be enhanced by conjugation to small drugs as antibody−drug conjugates (ADCs). The development of truly effective therapies for patients with treatment‐resistant cancers can be achieved by optimizing the various components of ADCs. Summary As the role of engineered antibodies in the development of various immunotherapeutic agents is now well established in the clinic, our aim is to investigate the potential and limitations of currently developed mAb‐based agents in improving cancer immunotherapy. With a narrative review of previous studies, it is hoped that these BsAbs, ICIs, and ADCs can be used as an efficient drug to target and treat human cancer while alleviating dangerous side effects in vivo.