Gene-edited and -engineered stem cell platform drives immunotherapy for brain metastatic melanomas.

ABSTRACT: Oncolytic virus therapy has shown activity against primary melanomas; however, its efficacy in brain metastases remains challenging, mainly because of the delivery and immunosuppressive nature of tumors in the brain. To address this challenge, we first established PTEN-deficient melanoma brain metastasis mouse models and characterized them to be more immunosuppressive compared with primary melanoma, mimicking the clinical settings. Next, we developed an allogeneic twin stem cell (TSC) system composed of two tumor-targeting stem cell (SC) populations. One SC was loaded with oncolytic herpes simplex virus (oHSV), and the other SC was CRISPR-Cas9 gene-edited to knock out nectin 1 (N1) receptor (N1^KO) to acquire resistance to oHSV and release immunomodulators, such as granulocyte-ma

SUBMITTER: Kanaya N 

PROVIDER: S-EPMC10799631 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature