Chimeric antigen receptor (CAR) T cell therapies have shown remarkable efficacy in haematological malignancies but demonstrate limited efficacy against solid tumours including prostate cancer. This is in part due to an immunosuppressive and fibrotic tumour microenvironment (TME) which leads to restricted CAR T cell tumour infiltration, reduced CAR T cell persistence and CAR T cell exhaustion. Accumulating evidence suggests that chemotherapies can modulate the TME to dampen immunosuppression and potentially improve CAR T cell efficacy.
Our work aims to optimise and develop an intravital imaging pipeline to both longitudinally image and assess changes in the TME following chemotherapeutic priming, and track CAR T cell infiltration in patient-derived xenograft (PDX) models of prostate cancer. To achieve this, we are using optical imaging windows in prostate cancer PDXs and repeated longitudinal imaging to assess tumour dynamics.
Using this imaging-based approach, we can detect any changes in fibrosis through second-harmonic generation (SHG) imaging, changes in blood vasculature using quantum dots, and assess CAR T cell dynamics in PDX models of prostate cancer following chemotherapy. This approach can enable us to optimise chemotherapeutic priming to modulate the TME and observe improvements in CAR T efficacy including cell tumour infiltration, persistence, movement and dwell time.
Our work highlights the advantages of optical imaging windows in guiding CAR T cell delivery and potentially improving response rates in solid tumors.