Antimelanoma immunotherapy: clinical and preclinical applications of IL-12 family members.
Malignant melanoma has been considered a prototypical 'immunogenic' tumor through clinical observations, such as the spontaneous regression of primary lesions, their higher incidence in immune-suppressed individuals, and the development of vitiligo after immunotherapy. Among many cytokines, IL-12 is one of the best characterized and the most potent anti-tumor cytokines. Although the systemic application of IL-12 resulted in disappointing results owing to its considerable toxicity, IL-12 is not entirely unusable in the clinical setting. IL-12-related cytokines, IL-23 and IL-27, have also been shown to possess anti-tumor activities in preclinical models. Although belonging to the same cytokine family, IL-12, IL-23 and IL-27 were found to have different anti-tumor mechanisms, adjuvant activity for tumor vaccines and adverse effects in a poorly immunogeneic melanoma model. In addition, their novel activities on melanoma have been clarified. We briefly review the key features of these members of the IL-12 cytokine family and discuss their potential relevance to melanoma immunity and antimelanoma immunotherapy.
Nagai
Hiroshi
H
Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. hnagai@med.kobe-u.ac.jp
Oniki
Shuntaro
S
Fujiwara
Susumu
S
Yoshimoto
Takayuki
T
Nishigori
Chikako
C
D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000627:therapeutic use*; D035843:Biomedical Research; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007167:Immunotherapy; D018664:Interleukin-12 / Q000276:immunology / Q000627:therapeutic use*; D053759:Interleukin-23 / Q000276:immunology / Q000627:therapeutic use; D007378:Interleukins / Q000276:immunology / Q000627:therapeutic use; D008545:Melanoma / Q000276:immunology* / Q000628:therapy*
D000970:Antineoplastic Agents; D053759:Interleukin-23; D007378:Interleukins; C464565:MYDGF protein, human; D018664:Interleukin-12