Despite significant improvements in detection and treatment, advanced prostate cancer remains incurable. When androgen receptor (AR)-targeted therapies fail, it is challenging to find new treatments to eradicate resistant tumours. Immunotherapy with genetically engineered chimeric-antigen receptor (CAR) T cells is a profound advance in cancer therapy. However, the suppressive tumour microenvironment (TME) is a significant barrier to CAR T cell efficacy in solid tumours, including prostate cancer. Here, we assessed the effectiveness of Lewis Y (LeY) CAR T cell therapy using patient-derived xenografts (PDXs) of prostate cancer from the Monash Urology Research Alliance (MURAL). As LeY is not a predicted target antigen for prostate cancer treatment, we first assessed the expression of LeY on 800 prostate cancer patient specimens plus 49 patient-derived xenografts (PDXs). LeY was expressed on 12% of localized and 20% of metastatic tumours, and in 57% of PDXs. In vitro, LeY CAR T cells directly killed organoids derived from AR-positive or AR-null PDXs. In vivo, LeY CAR T cells alone did not affect tumour growth, but a single prior dose of carboplatin resulted in tumour eradication. Carboplatin induced a pro-inflammatory TME that facilitated early and durable CAR T cell infiltration, including an altered cancer-associated fibroblast phenotype, enhanced extracellular matrix degradation and M1 macrophage differentiation. In a PDX less sensitive to carboplatin treatment, carboplatin did not boost CAR T cell infiltration; however, a reduction in tumour burden was still observed with increased T cell activation. Therefore, carboplatin improves the efficacy of CAR T cell treatment, with the extent of the response dependent on changes induced within the TME. As LeY expression was independent of AR expression, and both AR-positive and AR-null tumours were sensitive to LeY CAR T cells in vitro, LeY CAR T cells may provide a treatment option for patients who would not benefit from AR-directed therapies.