2016 Continuing Education Course:Unique Approaches to Safety Assessment of Gene, Cell, and Nucleic Acid-Based Therapies (Part 2)

Chairperson(s): Timothy MacLachlan, Novartis, Cambridge, MA; and Joy Cavagnaro, AccessBio, Boyce, VA.

Biotechnology Specialty Section Regulatory and Safety Evaluation Specialty Section

The platforms used for therapeutic treatment of disease have been greatly expanding over the last decade beyond the standard small molecule
approaches and the now widespread use of proteins and monoclonal antibodies. The prospect of gene therapy began several decades ago with the promise that misfunctioning genes could be simply replaced, but was stunted in its growth with several notable safety events in the clinic. Now gene therapy is making a furious comeback, with several industry and academic groups employing various technologies and racing to catch up. Cell therapy has experienced similar peaks and valleys in interest, with stem cells touted as a platform able to replace entire damaged organ systems. Multiple variants of what one would call a cell therapy now are in development ranging for treatment with fully differentiated somatic cells to naïve cells able to grow and differentiate in vivo. A combination of gene and cell therapy approaches is used in the widely popular T cell immunotherapy approaches for cancer treatment where cells are modified ex vivo to target tumors after reintroduction to the patient. Considering the potency of T cells it is not surprising that safety concerns have limited their target profile. Finally, the concept of knocking down expression of
gene expression has gained significant momentum with the introduction of therapeutic RNA interference and most recently with gene editing via a variety of methods. All of these “advanced therapy” platforms require very unique approaches outside of the standards defined by internationally
accepted guidance for preclinical safety assessment. Not only does the biopharmaceutical mantra of “case by case” apply, but standard issues
such as immunogenicity, tumorigenicity and appropriate animal models take on new meaning when applied to these therapies. With start-up
companies being formed and larger pharmaceutical companies investing heavily in these therapeutic areas, there is a growing need for toxicologists to be familiar with these platforms. This course will aim to introduce the audience to each of these four general categories of advanced therapies as well as provide a regulatory perspective on these modalities and
highlight where the standard approaches for safety assessment either do not apply or require unique application.