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IL-12 Vaccine Adjuvant |
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Vaxjo ID |
18 |
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Vaccine Adjuvant Name |
IL-12 Vaccine Adjuvant |
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Adjuvant VO ID |
VO_0001147
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Description |
IL-12 has been used as an adjuvant to cancer vaccination attempts in two settings. NIH3T3 cells transfected to produce IL-12 delayed the appearance of tumor when given along with irradiated BL-6 tumor cells, an aggressive and weakly immunogenic clone of B16 murine melanoma. Additionally, IL-12 given exogenously along with mutant p53 peptide was able to cause the regression of an established subcutaneous Meth A sarcoma (Rao et al., 1996). |
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Stage of Development |
Clinical Trial |
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Components |
Interleukin-12 is composed of two disulfide-linked subunits with molecular weights of 40 kDa (p40) and 35 kDa (p35). The human p35 and p40 subunits are structurally unrelated and have been mapped to chromosomes 3p12–3q13.2 and 5q31–q33, respectively. Cells require co-expression of both genes to secrete biologically active IL-12. IL-12 is primarily produced by phagocytic cells and antigen-presenting cells (APC) such as monocytes, DC and activated B lymphocytes, and production is strongly stimulated by infectious pathogens and their products. The other important stimuli for IL-12 synthesis are interactions between CD40 and its ligand (CD154), on APC and B cells or T cells, respectively (Portielje et al., 2003). |
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Dosage |
Mice were given IL-12 adjuvant at 0.5 mg (Rao et al., 1996). |
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Function |
In the vaccination area, IL-12 activates innate immune cells and promotes production of cytokines and chemokines, thereby mediating the attraction of other innate as well as specific immune cells to this region. We hypothesize that the co-administration of tumor antigens together with the strong pro-inflammatory cytokine IL-12 provides the environment with inflammatory danger signals required to activate antigen-presenting dendritic cells (DC) and prevents tolerance induction towards the tumor antigens. In addition, IL-12 directs the development of T-helper lymphocytes towards the type 1 (Th1) functional profile that promotes cellular immune responses and stimulates the proliferation of antigen-specific cytotoxic T lymphocytes (CTL) and thereby the establishment of immune memory (Portielje et al., 2003). |
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Safety |
Clinical experience in humans is still limited. Grade 2 or 3 toxicity (fatigue, depression and decreased numbers of peripheral blood cells) only occurs with the highest dose of IL-12 out of 0, 30, 100 and 300 ng/kg. IL-12 was administered subcutaneous (s.c.), adjacent to the vaccination site (Portielje et al., 2003). |
| Related Vaccine(s) |
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| References |
Portielje et al., 2003: Portielje JE, Gratama JW, van Ojik HH, Stoter G, Kruit WH. IL-12: a promising adjuvant for cancer vaccination. Cancer immunology, immunotherapy : CII. 2003; 52(3); 133-144. [PubMed: 12649742].
Rao et al., 1996: Rao JB, Chamberlain RS, Bronte V, Carroll MW, Irvine KR, Moss B, Rosenberg SA, Restifo NP. IL-12 is an effective adjuvant to recombinant vaccinia virus-based tumor vaccines: enhancement by simultaneous B7-1 expression. Journal of immunology (Baltimore, Md. : 1950). 1996; 156(9); 3357-3365. [PubMed: 8617961].
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