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 persistence, and exhaustion. Accumulating evidence suggests that chemotherapies can modulate the TME to dampen immunosuppression and potentially improve CAR T cell efficacy.

Our team has previously demonstrated that ‘priming’ the tumour with low-dose carboplatin prior to CAR T cell delivery significantly enhanced CAR T cell infiltration into solid tumours, reducing tumour size in patient-derived xenograft (PDX) prostate cancer models (Porter et al, Nature Communications, 2023). In order to understand how chemotherapeutic priming modifies CAR T cell behaviour and infiltration into prostate tumours, we have optimised and developed an intravital imaging pipeline to longitudinally image and track changes in the TME following chemotherapeutic priming, and track CAR T cell infiltration into the tumour.

Using this imaging-based approach, we can also detect any changes in fibrosis through second-harmonic generation (SHG) imaging, changes in blood vasculature using quantum dots, and assess CAR T cell dynamics. We demonstrate improved infiltration dynamics, including earlier and more extensive CAR T cell tumour infiltration as well as improved speed and kinetics in tumours that have been primed with low-dose carboplatin.

Our work highlights the advantages of optical imaging windows in guiding CAR T cell delivery and potentially improving response rates in solid tumors such as prostate cancer.