Cancer Gene Therapies: FDA Officials Highlight Regulatory Approaches

Posted 25 November 2015 By Zachary Brennan


As gene therapies begin to get a foothold among other cancer treatments, the US Food and Drug Administration (FDA) is taking a more flexible, data-driven approach for the preclinical testing programs of these biologically complex products, according to a new review from five FDA officials in Cancer Gene Therapy.

Although FDA has yet to approve a gene therapy to treat cancer, the authors note that about two-thirds of gene therapy clinical trials are for cancer treatments. In order to help industry and academia with these trials, the agency has released a number of guidance documents, including recent recommendations for microbial vectors used for gene therapy and how shedding studies for virus and bacteria-based gene therapies and oncolytic products should be designed.

The authors of the review note a number of key scientific and regulatory issues surrounding cancer gene therapies, including “the understanding of gene transfer vector biology, the safety of vectors in vitro and in animal models, optimum gene transfer, long-term persistence or integration in the host, shedding of a virus and ability to maintain transgene expression in vivo for a desired period of time.”

Regulatory Background

In the US, gene therapies are regulated by two federal agencies: FDA and the National Institute of Health’s Office of Biotechnology Activities (OBA). Gene therapy protocols are reviewed by the Recombinant DNA Advisory Committee (RAC), which is organized by OBA and cancer gene therapy products are evaluated by the Office of Cellular, Tissue and Gene Therapies (OCTGT) in the Center for Biologics Evaluation and Research (CBER). 

But according to the authors, FDA and RAC have overlapping review roles with clearly delineated responsibilities as both FDA and RAC consider preclinical and clinical trials.

On the manufacturing front, if the processes involve gene therapy vector products, vector production techniques and purification methods will be assessed by FDA. If the process involves ex vivo gene-modified cells, FDA will evaluate the method of cell collection/processing/culture conditions, irradiation of the tumor cells and final harvest of the cells.

Review of Therapies

The review from the FDA officials includes discussions on the different types of cancer gene therapy products that OCTGT regulates (see chart below), as well as key chemistry, manufacturing and controls (CMC) considerations, preclinical testing considerations, and clinical trial design and monitoring issues.

Viral Vectors Attenuated bacterial  vectors Viral Therapy  (oncolytic virus) Gene-Modified  Cells Nonviral  Vectors
 Retrovirus Listeria monocytogenes AdenovirusTumor cells, dendritic cells Plasmid vectors 
 Lentivirus Salmonella typhi and  Salmonella typhimurium VacciniaT-cell receptor  RNA
 Adenovirus  Herpes simplex virusChimeric antigen receptor T cells  Nanoparticles 
 Adeno-associated virus  Measles virus   
 Herpes simplex virus  Reovirus  
Pox viruses  

 Newcastle disease virus and polio  virus



“Past and current scientific advances have facilitated development of selectively targeted vectors that are efficient in gene transfer and reduce off-target effects,” the officials note. “Several different strategies for targeting tumors are being pursued, including gene delivery of tumor antigens and growth factors, gene-modified antigen-presenting cells, gene editing in vivo, gene interference by vectored RNA interference, suicide gene therapy, and native oncolytic viruses and bacteria, with or without genetic modifications.”

Cancer Gene Therapy

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Categories: Biologics and biotechnology, Blood, Human cell and tissue, Business Skills, Due Diligence, Preclinical, Quality, Regulatory strategy, News, US, FDA

Tags: cancer gene therapies, CBER, FDA regulations on gene therapy, regulatory issues for CBER

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