PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial

The dominant paradigm is the application of Chimeric Antigen Receptor (CAR) T cells for cancer treatment, specifically within the sub-paradigm of its use for solid tumors, exemplified by metastatic castration-resistant prostate cancer (mCRPC).

This Phase 1 clinical trial investigates PSCA-CAR T cell therapy for mCRPC, falling squarely within the 'normal science' stage of Kuhn's framework. The study operates under the established paradigm of CAR T cell therapy, aiming to refine and extend its application to a challenging solid tumor type. The research focuses on determining safety, dosage, and preliminary efficacy, characteristic of normal science puzzle-solving within a defined paradigmatic framework. While the study explores the novel application of PSCA-CAR T cells in mCRPC, it doesn't challenge the fundamental assumptions of CAR T cell therapy itself. The identified dose-limiting toxicity of cystitis and the exploration of strategies to mitigate it, alongside efforts to enhance CAR T cell persistence, further reinforce the 'normal science' classification. This work contributes to the incremental advancement and refinement of existing knowledge and techniques within the CAR T cell paradigm. There's a possibility of this research being classified as 'Model Drift', as the limited persistence of CAR T cells and the need for further optimization hints at the limitations of the current model when applied to mCRPC. However, the primary focus on safety and feasibility in a Phase 1 trial setting leans more definitively toward 'Normal Science'.