Adeno‐Associated Viral Vectors for Homology‐Directed Generation of CAR‐T Cells. Issue 1 (19th November 2019) - Moço, Pablo D.
Abstract: Immunotherapy with T cells expressing chimeric antigen receptors (CAR) is an emerging and promising treatment against refractory cancers. However, the currently adopted methods of modification of T cells pose a risk of insertional oncogenesis because lentiviral and retroviral vectors integrate the CAR transgene in a semi‐random fashion. In addition, this therapy is only available using autologous cells, which create problems in production and limit the access for patients who have their T cells depleted. One modification method that shows the ability to overcome both drawbacks is the knock‐in of the CAR simultaneously knocking‐out genes that prevent allogeneic therapy, such as the endogenous T cell receptor. In this mini‐review, the authors present recent efforts to develop safer universal CAR‐T cells. More specifically, the combined application of target‐directed nucleases, which create a double‐strand break at a specific genome locus, and the delivery of CAR DNA via adeno‐associated viral vectors for subsequent integration via homologous recombination and silencing of the targeted gene is focused on. Abstract : Currently available chimeric antigen receptor (CAR)‐T cell therapies are autologous, with cells coming from the patients themselves. If donor‐derived T cells are used, the T cell receptor present on their surface will recognize and attack the recipient's healthy tissues. Here, the authors present recent efforts to develop universal CAR‐T cells, via the combination of site‐specific nucleases and adeno‐associated viral vectors.