T-cell engineering for adoptive immunotherapy using tal-effector nucleases (TALEN)

Abstract

Encouraging data have emerged from adoptive T-cell therapies in advanced forms of cancer. Anti-tumor immunity is found in tumor infiltrating lymphocytes as well as engineered T cells where exogenous expression of a chimeric antigen receptor (CAR) confers cancer recognition on the cells. However, present adoptive immunotherapy methods are limited by the need for complex, time consuming, maninupaltion of autologous patient T-cells, and the use of cytotoxic lymphodepletion regimens to promote engraftment. To address these limitations Transcription Activator-like Effector Nucleases (TALEN), a novel class of sequence-specific nucleases created by the fusion of transcription activator-like effectors (TALEs) to the catalytic domain of an endonuclease, can be used to inactivate one or several genes in primary T cells. Use of these methods to engineer T-cells to enable an off-the-shelf therapeutic T-cell platform will be presented.