Development of antibody-targeted vaccines.
The use of monoclonal antibodies for immunotherapy has been validated by the commercialization of multiple monoclonal antibody products for oncology, infectious diseases and autoimmune diseases. In addition to their application as 'naked' antibodies, they have been used as delivery vehicles for cytotoxic agents to cancer cells. The exquisite specificity of antibodies can also be exploited to initiate and/or enhance the immune response to tumors or infectious agents by targeting the relevant antigen to antigen-presenting cells (APCs). Such antibody-targeted vaccines (ATVs) have demonstrated remarkable activity in preclinical models by eliminating the need for adjuvant and repetitive boosting, overcoming immunological non-responsiveness, inducing mucosal immunity and eliciting therapeutic cytotoxic T-cell-mediated antitumor effects. A variety of different receptors on APCs have been exploited for targeting antigens, which may allow optimization for specific immune responses. Selective targeting to appropriate receptors on APC subsets combined with strong activating signals is important for generating potent cytolytic T-cell responses. Studies have also suggested that ATVs may be selectively exploited to induce tolerance against antigens for treatment against transplant rejection or autoimmune diseases. The clinical development of this new class of antibody-based products has recently been initiated.
Keler
Tibor
T
Medarex Inc, 519 Route 173 West, Bloomsbury, NJ 08804, USA. tkeler@medarex.com
He
LiZhen
L
Graziano
Robert F
RF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D014612:Vaccines / Q000276:immunology / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D014612:Vaccines