Engineering lentiviral vectors for in vivo CAR T cell manufacturing

Autologous CAR-T cell therapy has transformed cancer treatments with durable clinical responses. Conventional CAR-T manufacturing is a complex multistep process that involves the genetic engineering of isolated patient T cells with viral vectors, followed by expansion ex vivo before infusion of the drug product. The cost of these therapies poses a significant challenge to their widespread application.

This project aims to reduce CAR T manufacturing costs by developing lentiviral vectors that can target specific subsets of T cells. If successful, these vectors could be used for the in vivo delivery of CAR encoding sequences directly to the T cells of patients.

Building on previous work from the Roddie/Pule group, the engineering of lentiviral vectors will be achieved by the passive incorporation of two proteins: a single chain variable fragment against a target-specific antigen and a pH-sensitive cell-penetrating peptide. These modified lentiviral particles will be tested for selective transduction of the naïve/central memory T cell compartment followed by efficient anti-tumour efficacy.

A broad range of skills are required for the project such as molecular cloning, cell culture, lentiviral vector production and purification, flow cytometry, and in vivo animal models.