Abstract
Idiotype (Id)-based immunotherapy has been exploited as cancer treatment option. Conceived as therapy for malignancies bearing idiotypic antigens, it has been also extended to solid tumors because of the capacity of anti-idiotypic antibodies to mimic Id-unrelated antigens. In both these two settings, efforts are being made to overcome the poor immune responsiveness often experienced when using self immunoglobulins as immunogens. Despite bearing a unique gene combination, and thus particular epitopes, it is normally difficult to stimulate the immune response against antibody variable regions. Different strategies are currently used to strengthen Id immunogenicity, such as concomitant use of immune-stimulating molecules, design of Id-containing immunogenic recombinant proteins, specific targeting of relevant immune cells, and genetic immunization. This review focuses on the role of anti-Id vaccination in cancer management and on the current developments used to foster anti-idiotypic B and T cell responses.
Highlights
Immunoglobulins (Ig) are glycoproteins formed by two identical heavy and two identical light polypeptide chains
Despite being self-proteins Ids can be immunogenic. For this reason Ids have been exploited as therapeutic immunogens in cancer treatment in two well-defined and clearly distinct contexts: (i) directly as a tumor-specific target on membrane Igpositive malignant B cells as a consequence of their clonotypic origin, and (ii) as surrogate of tumor-associated antigen (TAA) to induce specific immune responses (Figure 2)
The xenogeneic human IgG3 hinge/CH3 were required for good antibody responses and tumor protection in the murine MOPC315 myeloma and A20 B cell lymphoma models, with a DNA vaccine encoding the respective dimeric single chain Fv (scFv)-Id fused to the MIP-1α chemokine, administered by intramuscular injection followed by electroporation
Summary
Has been widely explored in cancer (Bhattacharya-Chatterjee et al, 2002; Lopez-Requena and Burrone, 2009). The xenogeneic human IgG3 hinge/CH3 were required for good antibody responses and tumor protection in the murine MOPC315 myeloma and A20 B cell lymphoma models, with a DNA vaccine encoding the respective dimeric scFv-Id fused to the MIP-1α chemokine, administered by intramuscular injection followed by electroporation. The immune response led to tumor protection in two murine models, the MOPC315 myeloma and the A20 B cell lymphoma (Fredriksen et al, 2006) It was demonstrated a superior priming capacity of APC derived from draining lymph nodes to activate antigen-specific T cells in vitro when animals were vaccinated with the MHC class II-specific plasmid. The 105AD7 mAb, which mimics the complement regulatory protein CD55 www.frontiersin.org
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