Research and Reports in Immunology

All submissions of the EM system will be redirected to Online Manuscript Submission System. Authors are requested to submit articles directly to Online Manuscript Submission System of respective journal.
Reach Us +1 (202) 780-3397

Mini Review - Research and Reports in Immunology (2022) Volume 5, Issue 1

The function of anti-mesothelin CAR T cells is improved by hairpin RNAs.

Hematologic malignancies have demonstrated good results with chimeric antigen receptor (CAR) T cell treatment. CAR T cells' antitumor activity, on the other hand, needs to be improved in order to improve therapeutic efficacy in hematologic and solid malignancies. On-target, off-tumor toxicity, antigen escape, short CAR T cell persistence, limited growth, trafficking to the tumour, and T cell activity suppression by an inhibitory tumour microenvironment are all challenges to overcome. Here, we'll look at how genetic engineering can be used to improve the antitumor efficacy of CAR T cell therapy in preclinical animals by refining the design of CAR T cells. The goal of this work was to see how targeted Tim3 knockdown affected the antitumor function of anti-mesothelin (MSLN)-CAR T cells. Three distinct shRNA sequences specific to different regions of the human Tim3 gene were developed and co-inserted into lentiviral vectors with an anti-MSLN-CAR transgene to knock down Tim3 expression. Tim3 expression was measured before and after antigen stimulation to determine the efficiency of Tim3 targeting in T cells. MSLN-CAR T cells and Tim3-targeted MSLN-CAR T cells were then examined for cytotoxic effects, proliferative response, and cytokine production. Tim3 was up-regulated when T cells and MSLN-CAR T cells were activated, according to our findings. In distinct groups of MSLN-CAR T cells, knocking down Tim3 resulted in a considerable reduction in its expression. Tim3 knockdown increased MSLN-CAR T cells' cytotoxic efficacy, cytokine generation, and proliferative ability. Tim3 knockdown increased MSLN-CAR T cells' cytotoxic efficacy, cytokine generation, and proliferative ability. Our findings suggest that inhibiting Tim3 signalling allows tumor-infiltrating CAR T cells that would otherwise be inactivated to continue to grow and perform effector activities, thereby changing the tumour microenvironment from immunosuppressive to immunosupportive.

Author(s): Stephanie Ryan

Abstract Full Text PDF

Get the App