Development of enhanced potency immunotherapy products using nonviral approaches

Author(s): James Brady, Linhong Li, Angelia Viley, Pachai Natarajan, Cornell Allen, Rama Shivakumar, Meg Duskin and Madhusudan V Peshwa*

In the next 5–10 years we could see cellular-based pharmaceuticals, or cell therapy, meeting the unmet medical needs of thousands of people. How this therapy will meet these needs depends on the ability of researchers and manufacturers to successfully and cost effectively manufacture and deliver engineered cell-based therapeutic products that are safe and exhibit enhanced potency with resulting durable, meaningful clinical efficacy. The ability to engineer such enhanced potency using nonviral, cGMP-compliant, automated and closed system manufacturing processes will represent a significant advantage. To outline how such a process might work, we have summarized the application of a scalable, cGMP-compliant, electroporation platform for engineering dendritic cells (DCs), NK cells and T cells for development of cellular immunotherapies targeting hematological malignancies and solid tumors. Autologous cellular immunotherapy refers to a class of therapies that are designed to stimulate a specific immune response against cancer cells or other disease targets. Many autologous cellular immunotherapy protocols involve ex vivo modification of a patient’s immune cells to enhance biological potency. Cellular modification strategies include pulsing DCs with tumor antigens/lysate and expression of chimeric antigen receptors or modified T-cell receptors (TCRs) on T cells and NK cells.