Details

Autor(en) / Beteiligte

• Salas-Mckee, January
• Kong, Weimin
• Gladney, Whitney L.
• Jadlowsky, Julie K.
• Plesa, Gabriela
• Davis, Megan M.
• Fraietta, Joseph A.

Titel

CRISPR/Cas9-based genome editing in the era of CAR T cell immunotherapy

Ist Teil von

• Human vaccines & immunotherapeutics, 2019-05, Vol.15 (5), p.1126-1132

Ort / Verlag

United States: Taylor & Francis

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Taylor & Francis Journals Auto-Holdings Collection

Beschreibungen/Notizen

• The advent of engineered T cells as a form of immunotherapy marks the beginning of a new era in medicine, providing a transformative way to combat complex diseases such as cancer. Following FDA approval of CAR T cells directed against the CD19 protein for the treatment of acute lymphoblastic leukemia and diffuse large B cell lymphoma, CAR T cells are poised to enter mainstream oncology. Despite this success, a number of patients are unable to receive this therapy due to inadequate T cell numbers or rapid disease progression. Furthermore, lack of response to CAR T cell treatment is due in some cases to intrinsic autologous T cell defects and/or the inability of these cells to function optimally in a strongly immunosuppressive tumor microenvironment. We describe recent efforts to overcome these limitations using CRISPR/Cas9 technology, with the goal of enhancing potency and increasing the availability of CAR-based therapies. We further discuss issues related to the efficiency/scalability of CRISPR/Cas9-mediated genome editing in CAR T cells and safety considerations. By combining the tools of synthetic biology such as CARs and CRISPR/Cas9, we have an unprecedented opportunity to optimally program T cells and improve adoptive immunotherapy for most, if not all future patients.