biotechnology advancement

Antigen-Mimic Single Domain Antibody (SdAb) Discovery

Full-length monoclonal antibodies have been highly successful as therapeutic agents against various immune diseases and cancers. However, the large size severely limits their applications. As an alternative, single domain antibodies (sdAbs) present great advantages as novel therapeutic agents, such as small size, high expression, improved robustness, and a large number of accessible epitopes.

Anti-idiotypic sdAb as Antibody Vaccine or Vaccine Vehicle
Immunotherapy based on the therapeutic antibody is one of the effective treatments; however, it still presents several possible limitations, including the need for repeating injection to achieve a lasting therapeutic effect, the potential drug resistance, and possible toxic effects on some patients. Anti-idiotypic sdAb which mimics epitope of a target protein (especially a toxin) can be used as a substitution for vaccination or as vaccine vehicle. Compared with conventional immunotherapy using therapeutic antibody and nominal antigen vaccine, it is a more attractive and promising approach. With proper design, such antigen-mimic anti-ID sdAb can induce a similar immune response with that triggered from nominal antigens and allows fewer injection doses than using therapeutic antibodies. Furthermore, it offers several main advantages in immunotherapy, including but not limited to:

Substitution of antigens which are from the non-protein origin, low or no immunogenic, or hard to be obtained
High specificity and affinity, non-toxicity, non-infectious, fewer side effects
Establishment of stable and robust humoral and/or cellular immune responses
Establishment of an immune memory response which persists after the end of treatment and prevents disease recurrence
Have the potential to act directly on the entire patient population (unrestricted by HLA type) and elicit immunity in the majority of the patients on vaccination
Overcome the problem of immune tolerance that is associated with most low or no immunogenicity tumor antigens and actively induces a protective response
A vaccine based on anti-idiotypic sdAb is quite a potential immunotherapy tool with excellent specificity, flexibility in design, and without toxicity. It shows extreme refolding capabilities, physical stability, and thermal stability; mimics small molecules and haptens which interact with crevices or cavities at the antibody surfaces in contrast to conventional antibodies.

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