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Immunogenicity Overview of Therapeutic Biologics

What is immunogenicity? The concept of immunogenicity is more complex. In the video, Immunogenicity is defined as the propensity of the therapeutic biologics to generate immune responses to itself and to related proteins or to induce immunologically related non clinical affect or adverse clinical events. <br>There are two types of immunogenicity in therapeutic biologics development process: wanted immunogenicity and unwanted immunogenicity<br>Wanted immunogenicity is typically related with vaccines, where the injection of an antigen (the vaccine) stimulates an immune response against the pathogen (virus, bacteria, cancer cell...) aiming at protecting the organism. Unwanted immune responses to therapeutic biologics may also neutralize their biological activities and result in adverse events not only by inhibiting the efficacy of the therapeutic biologics, but also by cross-reacting to an endogenous protein counterpart, leading to loss of its physiological function (e.g., neutralizing antibodies to therapeutic erythropoietin cause pure red cell aplasia by also neutralizing the endogenous protein). The meaning of immunogenicity in this overview is the latter adverse immune response in the therapeutic biologics discovery and development.<br><br>

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Immunogenicity Overview of Therapeutic Biologics

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  1. Immunogenicity Overview of Therapeutic Biologics

  2. What is Immunogenicity? The propensity of the therapeutic biologics to generate immune responses Wanted immunogenicity Unwanted immunogenicity

  3. Background of Immunogenicity-APC Antigen presentation T cell epitopes Phagosome Antigen + APC Endosome/lysosome <34 AA peptides Golgi apparatus Endoplasmic reticulum Secrete vesicles MHC II Affinity of peptides and MHC MHC II CD4+T DC-T cell assay Surface of APC Peptide-MHC-II complex

  4. Background of Immunogenicity-ADA x

  5. Importance of Immunogenicity in Therapeutic Biologics Development

  6. Importance of Immunogenicity in Therapeutic Biologics Development

  7. Impact of Immunogenicity • Effects on bio-availability EX. 1: first generation therapeutic mAbs • Effect on Safety and Efficacy EX. 2: terminate the development  • Effect on PK including potential cross reactivity to endogenous proteins Inhibition of the function of endogenous protein Injection site reactions Systemic reactions mild or life threatening Formation of ADA (HAMA, HACA, HAHA) Formation of neutralizing antibodies Formation of immune complexes Formation of anti-idiotypic antibodies

  8. Immunogenicity Assessment • Strategy-SIAT ®

  9. Immunogenicity Assessment • Strategy - SIAT ® ADA Assay x x x Detect with labeled (e.g. biotinylated drug) Add serum containing Anti-drug antibodies Immoblize drug

  10. Immunogenicity Assessment Strategy - SIAT ® De-immunization Service Locate T cell epitopes 3D model of Fvdomain (of the antibody) Multiple sequence alignmets(of human and murine) Tcell epitopes Compatibility with the 3D structure Replace T cell epitopes Affinity with HLA allotype

  11. Contact us Address: 45-1 Ramsey Road, Shirley, NY 11967, USA Tel:1-631-871-5806Fax:1-631-207-8356Email: info@creative-biolabs.com Web: www.creative-biolabs.com

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