Day 1 :
Keynote Forum
Jianyong Wang
Genentech, USA
Keynote: Fit–for-purpose immunogenicity assessment for theraputic antibodies in non-clinical studies
Biography:
Jerry Wang received his PhD from the Deaprtment of Biochemistry and Molecular Biology at Medical Univisity of Ohio (Toledo, OH). After post-doctoral studies at Univsersity of Michigan Medical Center, he began his industry career as a pharmacologist. He is currently a scientist in the Department of Biochemical and Cellular Pharmacology at Genentech. His group supports the therapeutic antibody programs during research and early development phases. His main responsibilities include antibody screening and characterization by in vitro and in vivo studies to select clinical candidates. He has worked in biopharmaceutical industry for more than 15 years including 10 years at Genentech for biotherapeutics R&D.
Abstract:
Assessing immunogenicity, the propensity of a therapeutic protein product (including antibody drugs) to generate immune responses or to induce immunologically related adverse events, is recommended during the development phase of a biotheraputic drug. Even though immunogenicity assessment in nonclinical animal studies are not relevant in predicting potential immunogenicity in humans, it can still be very useful in assisting the interpretation of PK/PD/TK study results. This is because for non-clinical studies, immunogenicity can impact exposure (PK), response (PD & efficacy), and safety
(toxicity and adverse events). Thus immunogenicity assessment, i.e. measurement of anti-drug antibodies (ADA), should be evaluated when there are evidence of altered PD activity; unexpected changes in drug exposure in the absence of a PD marker; or evidence of immune-mediated reactions (immune complex disease, vasculitis, anaphylaxis, etc.). In this presentation, several commonly used ADA assay formats and technology platforms will be reviewed. Key assay design elements and assay development procedures, including approaches that improve ADA assay drug tolerance, will be discussed in detail. We will also share ADA results from three monkey PK/PD case studies by comparing different ADA assay formats. Lastly, we will recommend fit-for-purpose strategies of ADA assay development and characterization for non-clinical animal studies.
- Medicinal Chemistry | Clinical Chemistry | Forensic Chemistry | Natural Chemistry | Electrochemistry | Geochemistry | Oncolytic Virotherapy | Immunopharmacotherapy | Analytical Biotherapeutics
Location: Dallas
Chair
Montasser Altorgoman
Alexandria University, Egypt
Session Introduction
Jianyong Wang
Genentech, USA
Title: Combining immunoassay and LC/MS to characterize stability of antibody therapeutics In Vivo
Biography:
Jerry Wang received his PhD from the Deaprtment of Biochemistry and Molecular Biology at Medical Univisity of Ohio (Toledo, OH). After Post-doctoral studies at Univsersity of Michigan Medical Center, he began his industry career as a Pharmcologist. He is currently a Scientist in the Department of Biochemical and Cellular Pharmacology at Genentech. His group supports the therapeutic antibody programs during research and early development phases. His main responsibilities include antibody screening and characterization by in vitro and in vivo studies to select clinical candidates. He has worked in biopharmaceutical industry for more than 15 years including 10 years at Genentech for biotherapeutics R&D.
Abstract:
As many of therapeutic biologics (including monoclonal antibodies and antibody-drug conjugates) enter the frontline of disease treatment, tracking their stability in vivo, is a critical step in development of these therapeutics. Unstable antibody therapeutics (including unstable antibody-drug conjugates) may cause decreased drug activity, fast clearance, increased immunogenicity, and safety issues (toxicities). Non enzyme-mediated deamidation is a common protein degradation that normally occurs on asparagine (and to a lesser extent, glutamine residues), resulting in a conversion to aspartic and isoaspartic
acids with a mass shift of +0.984 Da. To monitor the deamidation of therapeutic antibodies dosed in vivo, we developed analytical methods with the combination of immunoassay and LC/MS using peptide level MS detection. We further optimized the process and established an automated high throughput method allowing for high fi delity deamidation analysis of human
antibodies from in vivo study samples. Similarly, we were also able to characterize the stability of antibody-drug conjugates in vivo, by using the combination of affi nity-capture and intact protein MS analysis. Th ese procedures will help to exclude unstable drug candidates at early development phase, and select stable antibody-based therapeutics for clinical applications.
Biography:
Montasser Altorgoman, is currently a PhD candidate at the Alexandria University, Egypt Faculty of Science, Department of biochemistry. In addition he is as a biochemist at the Toxins lab at the Ministry of health. Since the usage of Interferon for treatment of Virus C patients specially genotype 4 is inevitable, so the question is could be the side effects of the Interferon prohibited and the contraindications to the Interferon treatment might be evaded. Hence his all focus is for fi nding new techniques like liposomal delivery and/or a new adjuvant therapy specially the natural ones to ameliorate side effects of the treatment.
Abstract:
Liver fi brosis is the wound healing response to a variety of acute or chronic stimuli, for instance viral infection, toxins and metabolic diseases. Th e pattern of hepatic stellate cell activation provides an important framework to pinpoint
sites of antifi brotic therapy. IFN exhibit a wide spectrum of biological activities in target cells including antiviral, immunomodulatory, anti angiogenic and growth-inhibitory eff ects. Th e antiproliferative eff ects of IFN are the rational basis for their use in the treatment of metastatic malignant melanoma and renal cell carcinoma. Th e food use of S. oleraceus is justifi ed
by the high content of vit. C, fl avonoids and phenolics. Th e previous studies discussed the antifi brotic eff ect of IFN and S. oleraceus individually on liver fi brosis but in this study the combination treatment has been studied well in the induced liver fi brosis models. Using diff erent immunoassays, histopathol-ogy, colorimetric and PCR techniques results obtained showed that TAA causes hepatic fi brosis by induction of free radical production and decrease cellular antioxidant stores. Th e different treatment ways including combination treatment group showed a signifi cant inhibi-tory eff ect in targeting hepatic fi brosis by reducing oxidative stress, increasing the activity of antioxidant enzymes and by inhibiting HSCs infl ammation, activation
and proliferation through increasing the levels of antifi brotic co-transcription factor PPAR-γ and decrease the levels of the main HSCs fi brogenic cytokines TGFβ1 and PDGF-BB. In conclusion, bio-chemical, molecular and histopathological fi ndings demonstrated that the combination treatment improved the antifi brotic eff ect better than the individual one, the prophylactic usage of SE protected against hepatic fi brosis and SE had no side eff ect.