Exploring novel targets for CAR-T Therapy for Prostate Cancer

ConclusionWe generated a second-generation CAR targeting either Lewis Y or GRP-78 with a truncated CD34-tag for purification. Because the differentiation and phenotype of the CAR-T product may have a critical impact on the post-infusion antitumor effect and persistence of the cells, we also investigated the phenotype of CAR-T product with different γc cytokines, i.e. IL-2, IL-7 and IL-15, to generate early differentiation stage cells with less exhaustion phenotypes. In the optimized protocol, by using the retroviral transduction system, starting from 3 × 107 PBMC, we're now able to produce approximately 109 bulk CAR-T cells or 5 × 108 purified CAR-T cells with over 98% purity, within 7-10 days. Furthermore, most of these cells remained early naïve or memory-like phenotype. These engineered T cells are capable to eradicate prostate cancer tumour cells in vitro and to secrete TNF-α and IFN-γ cytokines. The in vivo study also showed that the infused cells can reduce the tumour burden and persist post infusion.Our results demonstrate that the novel CAR-T cells exhibited specific and efficient tumoricidal effect against prostate cancer cells. Furthermore, by introducing the CD34-tag, with the optimized protocol, we're now able to produce CAR-T cells with high purity and more early differentiation stage in a relatively shorter time. This may further benefit the clinical application of CAR-T therapy, by reducing the total number of the infused cells and shortening the ...
Source: Cytotherapy - Category: Cytology Source Type: research