Enhancing mesothelin CAR T cell therapy for pancreatic cancer with an oncolytic herpes virus boosting CAR target antigen expression.

ABSTRACT: Mesothelin (MSLN) is a prominent target antigen for CAR T cell therapy due to its extensive expression in various solid tumors, including pancreatic cancer. However, the therapeutic efficacy of MSLN-targeted CAR T cell therapy has been limited in clinical trials for pancreatic cancer, often resulting in temporary stable disease as the best response. The heterogeneous expression of MSLN and its loss over time, along with the immunosuppressive tumor microenvironment (TME), are key factors restricting effectiveness. Oncolytic viruses are emerging cancer therapies that replicate in tumor cells and remodel the TME into an immunogenic state. Here, we engineered an oncolytic herpes simplex virus type 1 expressing human MSLN (HSV-MSLN) and evaluated its combination with MSLN-CAR T cells in a murin

SUBMITTER: Aboalela MA 

PROVIDER: S-EPMC12078189 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature