Effective cancer therapy through immunomodulation.
MAbs directed toward tumor cells, tumor neovasculature, and host negative immunoregulatory elements (checkpoints) have emerged as useful immunotherapeutic agents against cancer. However, effective active modulation of the immune response with anticancer vaccines will require identifying appropriate tumor-rejection antigens; optimizing the interactions of peptides, antigen-presenting cells, and T cells; and blockading negative immunological checkpoints that impede an effective immune response. Checkpoints being targeted include CTLA-4 and PD1 that are negative signaling receptors expressed on activated T cells, CD4+CD25+ Foxp3-expressing Tregs (suppressor T cells), IL-2-mediated activation-induced cell death (AICD), and the cytokine TGFbeta.
Waldmann
Thomas A
TA
National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1374, USA. tawald@helix.nih.gov
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D000954:Antigens, Surface / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D060908:CTLA-4 Antigen; D019496:Cancer Vaccines; D016207:Cytokines / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D061026:Programmed Cell Death 1 Receptor; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D019496:Cancer Vaccines; D016207:Cytokines; D007155:Immunologic Factors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D016212:Transforming Growth Factor beta