CRISPR-Cas, a robust gene-editing technology in the era of modern cancer immunotherapy
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Cancer Cell International Open Access
REVIEW
CRISPR‑Cas, a robust gene‑editing technology in the era of modern cancer immunotherapy Seyed Mohammad Miri1, Elham Tafsiri2, William Chi Shing Cho3 and Amir Ghaemi4*
Abstract Cancer immunotherapy has been emerged as a promising strategy for treatment of a broad spectrum of malignancies ranging from hematological to solid tumors. One of the principal approaches of cancer immunotherapy is transfer of natural or engineered tumor-specific T-cells into patients, a so called “adoptive cell transfer”, or ACT, process. Construction of allogeneic T-cells is dependent on the employment of a gene-editing tool to modify donor-extracted T-cells and prepare them to specifically act against tumor cells with enhanced function and durability and least sideeffects. In this context, CRISPR technology can be used to produce universal T-cells, equipped with recombinant T cell receptor (TCR) or chimeric antigen receptor (CAR), through multiplex genome engineering using Cas nucleases. The robust potential of CRISPR-Cas in preparing the building blocks of ACT immunotherapy has broaden the application of such therapies and some of them have gotten FDA approvals. Here, we have collected the last investigations in the field of immuno-oncology conducted in partnership with CRISPR technology. In addition, studies that have addressed the challenges in the path of CRISPR-mediated cancer immunotherapy, as well as pre-treatment applications of CRISPR-Cas have been mentioned in detail. Keywords: Cancer immunotherapy, CRISPR-Cas, Cas9, TCR T-cell, CAR T-cell, Allogeneic T-cell Background According to statistics, the appearance of about 18.1 million newfangled cancer victims and 9.6 million cancerrelated fatalities just in 2018 is entirely self-explanatory of the importance of developing more efficient cancer therapy strategies [1]. Besides the well-known approaches of cancer therapy such as chemotherapy, radiotherapy, surgery, as well as the latest methods such as oncolytic virotherapy, harnessing the immune system against cancer cells has been developed [2, 3]. Engineered T-cell’s anti-cancer properties have expanded the application of immunotherapy from viral infections to cancer treatment
*Correspondence: [email protected]; [email protected] 4 Department of Virology, Pasteur Institute of Iran, Tehran, P.O.Box: 1316943551, Iran Full list of author information is available at the end of the article
[4]. Adoptive cell transfer (ACT) cancer immunotherapy can be done through deployment of three different immunogenic constructs including tumor-infiltrating lymphocytes (TILs), T-cell receptor (TCR) T-cells, and engineered chimeric antigen receptor (CAR) T-cells [5]. To achieve desired CAR T-cells or to modify TCR T-cells, incorporation of a gene-engineering tool is needed. Clustered regularly interspaced short palindromic repeats (CRISPR) in association with Cas nuclease stands out from other gene-editing methods, such as zinc finger nucleases (ZFNs) and transcription activator-like effector nuc
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