Immunocytokines: amplification of anti-cancer immunity.
Many cancers elicit an anti-tumor immune response, which is nevertheless unable to protect the patient. One approach to boost anti-tumor immunity is to target immunostimulatory cytokines to the tumor. Such targeting can be achieved by generating chimeric proteins (immunocytokines) in which the cytokine in question is fused to the C-terminus of a tumor-specific antibody. Immunocytokines containing interleukin-2 (IL-2) have been efficacious in mouse tumor models and have entered clinical trials. Numerous enhancements of immunocytokines are possible, including use of additional stimulatory cytokines, alternate modes of tumor targeting, structural modifications to improve pharmacokinetics, and removal of potentially immunogenic sequences from the fusion protein. In addition, immunocytokines are likely to be efficacious in combination with other therapies, including some forms of chemotherapy and cancer vaccines.
Davis
Craig B
CB
EMD Lexigen Research Center, Billerica, MA 01821, USA. cdavis@emdlexigen.com
Gillies
Stephen D
SD
D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry* / Q000502:physiology; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D017434:Protein Structure, Tertiary; D011961:Receptors, Fc / Q000737:chemistry; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism
D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D007376:Interleukin-2; D011961:Receptors, Fc; D011993:Recombinant Fusion Proteins