The Remarkable Proliferation of Cancer Immunotherapies

Key Points:

• It has been 15 years since the first immune checkpoint inhibitor (anti-CTLA-4) was FDA-approved to extend survival in metastatic melanoma, marking a turning point in cancer immunotherapy with the 2013 recognition of immune checkpoint inhibitors and CAR-T therapies.
• The cancer immunotherapy field has expanded rapidly, with over 2,500 drugs and programs in development, including checkpoint inhibitors, antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), CAR-T and CAR-NK therapies, oncolytic viruses, and cancer vaccines for treatment and prevention.
• Immune checkpoint inhibitors like pembrolizumab have multiple FDA approvals but show only partial and variable patient responses, prompting development of new checkpoint targets (e.g., TIGIT, LAG-3) and combination therapies to overcome resistance.
• Advances in cell therapies include engineered CAR-T cells, tumor-infiltrating lymphocytes (TILs), and emerging off-the-shelf allogeneic CAR therapies using viral or mRNA delivery systems, aiming to reduce costs and improve accessibility.
• Future progress depends on improved biomarkers and immune system assessments, such as thymus health scoring and non-invasive tumor microenvironment profiling via liquid biopsy and AI, to better guide personalized immunotherapy and expand preventive vaccine strategies for high-risk individuals.