Clinical Development Of CRISPR-Based Therapies In Oncology

CRISPR/Cas9 gene editing techniques hold the potential to unlock significant advances in oncology drug development. However, the novelty of CRISPR-based therapies creates unique operational challenges that impact the design and execution of clinical trials. The innate immunogenicity to bacteria-derived Cas proteins and certain delivery vectors necessitates examination of regional differences in immunological responsiveness and methods of gene product delivery. This requirement must be coordinated with the demands of IP management, which for cell based therapy modified by CRISPR technology may involve the collection of samples from donors, as well as the shipment of samples to other locations for testing, transfection, and expansion. The edited genetic material must then be returned to the trial sites and reintroduced to the participants, while maintaining favorable storage for cell or vector viability. Reintroduction of the modified genetic materials may involve invasive procedures, highlighting ethical concerns for investigators and institutional review boards overseeing controlled trials, and the importance of clinical trial infrastructure and operational competency with surgical techniques at selected centers. Because these therapies involve genetic changes that may induce proliferation, differentiation, or migration of cells, regulators appropriately require additional safety data before authorization for use and during use in the clinic. The design of clinical development programs that can acknowledge and anticipate evolving standards for clinical research in an era of advanced therapy medicinal products is an overarching mandate both of sponsors, and their associated partners in clinical development.