Outlining Novel Cellular Adjuvant Products for Therapeutic Vaccines Against Cancer

Josianne Nitcheu Tefit; Vincent Serra


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

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Adjuvant & Therapeutic Cancer Vaccine Development

In cancer immunization, the primary lymphocyte population that is widely recognized to be the necessary target for effective cancer therapeutic vaccine strategies is the CD8+ T cells.[2] With regard to cancer antigens, adjuvants are needed to boost the desired immune response to weak antigens. Such adjuvants are necessary to increase the response to the vaccines by stimulating a potent functional CD8+ T-cell response in patients who respond poorly to the relevant tumor. Adjuvants commonly found in modern vaccines include active immunostimulants, defined as components that directly engage the immune system to increase responses to antigens; carriers, which are highly immunogenic foreign proteins such as tetanus toxoid or keyhole limpet hemocyanin (KLH) that provide T-cell help to poorly immunogenic tumour-derived or other pathogen-associated antigens; and vehicle adjuvants, which are oil emulsions or liposomes consisting of lipid layers that can encapsulate antigens and act as antigen delivery vehicles as well as stimulating the immune response.[3] There have been various attempts to classify adjuvants and probably the most commonly applied classification system is based on the underlying mechanisms by which they act.[4,5] However, adjuvants act by several different mechanisms, which makes their classification rather complex and subjected to regular redefinitions as additional innate pathways of immunity are discovered. Vaccine adjuvants are characterized by different classes of compounds, such as alum salts and other mineral adjuvants, tensoactive agents, bacterial derivatives, vehicles and cytokines. However, related compounds frequently have antagonizing immunomodulating properties; for example, the capacity to stimulate Th1 or Th2 immunity. Adjuvants such as MF59® (Novartis Vaccines and Diagnosis) and immunostimulatory complexes (ISCOMs) enhance T-cell and antibody responses without altering their Th1/Th2 cell balance of the specific antigen. More polarized Th1-cell responses are elicited by adjuvants that incorporate agonists of Toll-like receptor (TLR)-3, TLR-4, TLR-7/8 and TLR-9, while complete Freund's adjuvant (CFA) induces mixed Th1 and Th17 responses.[6]


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