Outlining Novel Cellular Adjuvant Products for Therapeutic Vaccines Against Cancer

Josianne Nitcheu Tefit; Vincent Serra


Expert Rev Vaccines. 2011;10(8):1207-1220. 

In This Article


Cytokines are included in the modern classification of adjuvants. Cytokines, such as IL-2, GM-CSF, IL-12 and several others, have been used as adjuvants in cancer vaccines.[123] IFN-γ is a pleiotropic cytokine able to enhance cellular immune responses through a variety of mechanisms.[124] GM-CSF enhances the primary immune response by activating and recruiting APCs.[125] IL-12 is an exceedingly potent immune adjuvant and promotes IFN-γ release by IL-12 receptor-expressing T and natural killer (NK) cells and induces Th1 polarization, as well as proliferation of IFN-γ-expressing T cells.[14,126–129] Cytokines are seen to have particular potential in DNA vaccines where the cytokine can be expressed by the same vector as the antigen. Although GM-CSF is currently the cytokine most frequently used as an adjuvant for cancer vaccines, its practical application has been limited by the requirement for multiple doses, toxicity and the immunogenicity of heterologous cytokines.[97] The possible clinical use of IL-12 as an adjuvant for cancer vaccines was investigated in a Phase II trial with Melan-A peptide-pulsed peripheral blood mononuclear cell in association with recombinant human IL-12 in patients with advanced melanoma. Intermediate doses of IL-12 induced remarkable peptide-specific CD8+ T-cell responses, demonstrating the possibility of finding nontoxic doses of IL-12 that exert adjuvant activity.[126] Other cytokines, such as IL-7, -15 and -21, have demonstrated a potent vaccine adjuvant effect in tumor models and are being used in the context of cancer immunotherapy.[130] As discussed earlier, careful clinical trials will be needed to identify appropriate doses and regiment for the treatment of cancer with these novel immunomodulators.


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