Journal for immunotherapy of cancer
Clonal circulating tumor cell mobilization following chimeric antigen receptor T-cell therapy in metastatic castration-resistant prostate cancer
By Pham DM, Rivera A, Lin A and 8 others.
Abstract
Background
Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive, treatment-refractory stage of disease with limited treatment options and poor prognosis. Chimeric antigen receptor (CAR)-T cell therapy has demonstrated success in hematological malignancies. However, responses in solid tumors remain variable, underscoring the need for improved real-time monitoring of tumor biology and therapeutic response.
Methods
In this exploratory, retrospective analysis within a CAR-T clinical trial (NCT03873805), we characterized the circulatory tumor landscape of mCRPC using a high-resolution, single-cell, enrichment-free liquid biopsy platform integrating phenotypic and genomic profiling of circulating tumor cells (CTCs) and other rare cells. Longitudinal peripheral blood (PB) and bone marrow aspirate (BMA) samples were collected from eight patients (four clinical responders, four non-responders) before lymphodepletion (LD), before infusion, and after therapy. Fluorescent whole-slide imaging was used to identify rare cell phenotypes, and single-cell whole-genome copy-number variation profiling was performed to assess clonal identity.