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 TGFβ.