CONFERENCE SERIES: Biological Therapeutic Products
Recorded at: PEGS: The Essential Protein Engineering Summit
Digital Course: How Size Matters in Therapeutic Antibody Design
About this Product:
Harnessing antibodies’ innate nature to specifically deliver a therapeutic to its target has brought about a multi-billion dollar revolution in biomedicines. Two international giants in antibody therapeutics, K. Dane Wittrup and David Blakey, come together to discuss an over-arching concern in the development of biologics: How antibody size affects efficacy, distribution and half-life. This digital course explores the strategies for designing antibody therapeutics, and examines how the size of the molecule affects penetration and distribution into tissues and tumors.
About this Product:
Over 86 Minutes
Site License: $1380
Agenda At A Glance:
Practical Theoretic Guidance for the Design of the Size and Binding Affinity of Tumor Targeting Agents: IgGs Win
K. Dane Wittrup, Ph.D., C.P. Dubbs Professor, Chemical Engineering & Biological Engineering, Associate Director, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
Theoretical analyses of targeting agent pharmacokinetics provide specific guidance with respect to desirable design objectives. In short, IgG-sized macromolecular constructs exhibit the most favorable balance between systemic clearance and vascular extravasation, resulting in maximal tumor uptake. Quantitative predictions of the effects of dose and binding affinity on tumor uptake and penetration are also provided. The single bolus dose required for saturation of xenografted tumors in mice can be predicted from knowledge of antigen expression level and metabolic half life. The role of high binding affinity in tumor uptake can be summarized as: essential for small peptides, less important for antibodies, and irrelevant for nanoparticles.
Biography: Professor K. Dane Wittrup is the Joseph R. Mares Professor of Chemical Engineering and Biological Engineering at the Massachusetts Institute of Technology, a position he has held since 1999. From 1989-1999 he was Assistant Professor, Associate Professor, and then J. W. Westwater Professor of Chemical Engineering, Bioengineering, and Biophysics at the University of Illinois in Champaign/Urbana.
Prof. Wittrup received a B.S. in Chemical Engineering Summa cum Laude in 1984 from the University of New Mexico, and a Ph.D. in Chemical Engineering from the California Institute of Technology in 1988 under the thesis direction of Prof. James Bailey. Following a year of postdoctoral research at Amgen (Thousand Oaks, CA), Dr. Wittrup joined the faculty at the University of Illinois. Wittrup’s research program is focused on protein engineering of biopharmaceutical proteins by directed evolution. Areas of interest include: pretargeted radioimmunotherapy; biological response modification of EGFR; and immunotherapy of cancer via engineered cytokines and vaccines.
Prof. Wittrup has received the following awards and honors recognizing his scholarship: the A. McLaren White Award, for First Prize in the National American Institute of Chemical Engineers Student Design Contest (1984); the Presidential Young Investigator Award of the National Science Foundation (1990-1995); the Allan P. Colburn Award of the American Institute of Chemical Engineers, for excellence in publications for an individual under the age of 35 (1998); the University of New Mexico College of Engineering Distinguished Young Alumnus Award (2000); the Dow Chemical Company Teaching Award(1989); the UIUC School of Chemical Sciences Award for Excellence in Teaching (1993); the UIUC College of Engineering Anderson Award for Undergraduate Advising (1991, 1994); the J.R. Mares Professorship (1999- ); and induction as a Fellow of the American Institute of Medical and Biological Engineers (1999).
Prof. Wittrup has mentored the following Ph.D. students and postdoctoral fellows who are now faculty members: Jennifer Cochran (Bioengineering, Stanford University); Anne Robinson (Chemical Engineering, University of Delaware); Eric Boder (Chemical Engineering, University of Pennsylvania); Eric Shusta (Chemical Engineering, University of Wisconsin, Madison); Jennifer van Antwerp (Chemical Engineering, Calvin College); Balaji Rao (Chemical Engineering, North Carolina State University); Yong-Sung Kim (Biotechnology, Ajou University, Korea); Mark Olsen (Biochemistry, Texas A & M, Amarillo).
Tumor Penetration of Therapeutic Antibodies – Implications for Cancer Therapy
David Blakey, Ph.D., Chief Scientist, Oncology iMed, AstraZeneca
The ability of intact antibodies and fragments to access tumor cells distant from the tumor blood supply is an important therapeutic consideration for antibody based oncology drugs. Preclinical and clinical data on antibody distribution within tumors will be reviewed and the implications for therapy will be discussed.
Biography: Dr Blakey has over 20 years experience in therapeutic antibodies. He worked on the optimisation and pharmacology of ricin immunotoxins at the ICRF and then joined AstraZeneca in 1987 where he initially worked on the development of immunotoxins and then on Antibody Directed Enzyme Prodrug therapy in collaboration with the Cancer Research Campaign. More recently Dr Blakey led the establishment and scientific leadership of AstraZeneca’s antibody collaboration with Abgenix/Amgen as well as having a science leadership role within AstraZeneca in the area of therapeutic vascular modulation. In his current role Dr Blakey provides global oncology scientific discovery leadership across both Small Molecule and Biologics projects.
About the Conference:
PEGS is the essential antibody and protein engineering event of the year, where what you learn can be directly applied to your work. The event provides 1,200+ participants to network with their peers and learn about unpublished science in the session rooms. Delegates engage in problem solving breakout discussions and gain insight from over 60 exhibitors, and view the 155 posters in the exhibit hall.