IL-12: a promising adjuvant for cancer vaccination.
The clinical development of interleukin 12 (IL-12) as a single agent for systemic cancer therapy has been hindered by its significant toxicity and disappointing anti-tumor effects. The lack of efficacy was accompanied by, and probably related to, the declining biological effects of IL-12 in the course of repeated administrations at doses approaching the maximum tolerated dose (MTD). Nevertheless, IL-12 remains a very promising immunotherapeutic agent because recent cancer vaccination studies in animal models and humans have demonstrated its powerful adjuvant properties. Therefore, IL-12 may re-enter the arena of cancer therapy. Here, we review the immune modulating characteristics of IL-12 considered responsible for the adjuvant effects, as well as the results of animal and human cancer vaccination studies with IL-12 applied as an adjuvant. In addition, we discuss how studies with systemic IL-12 in cancer patients, and several other lines of evidence, indicate that IL-12 may exert optimal adjuvant effects only at low dose levels. Therefore, the MTD may not constitute the maximum effective dose of IL-12 for adjuvant application.
Portielje
Johanna E A
JE
Department of Medical Oncology, Erasmus Medical Center, Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
Gratama
Jan Willem
JW
van Ojik
Heidi H
HH
Stoter
Gerrit
G
Kruit
Wim H J
WH
D000818:Animals; D019496:Cancer Vaccines; D017024:Chemotherapy, Adjuvant; D003713:Dendritic Cells; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D007249:Inflammation; D018664:Interleukin-12 / Q000378:metabolism / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000378:metabolism; D020714:Maximum Tolerated Dose; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D019496:Cancer Vaccines; D011994:Recombinant Proteins; D018664:Interleukin-12