Urinary cytomegalovirus excretion: The unresolved issues.

Cytomegalovirus (CMV) excretion in urine is frequently observed in clinical practice. However, the specific circumstances and pathophysiological mechanisms underlying this shedding remain largely unknown. Here, we address some of the key questions regarding urinary CMV excretion, focusing on new hypotheses raised by recent advances in the field. Cellular origins of CMV shedding, clinical contexts of occurrence, systemic spread of the virus versus compartmentalization in the urinary tract, and clinical impact are successively discussed.

Umbilical Cord Blood as a Source of Less Differentiated T Cells to Produce CD123 CAR-T Cells.

Chimeric Antigen Receptor (CAR) therapy has led to great successes in patients with leukemia and lymphoma. Umbilical Cord Blood (UCB), stored in UCB banks, is an attractive source of T cells for CAR-T production. We used a third generation CD123 CAR-T (CD28/4-1BB), which was previously developed using an adult's Peripheral Blood (PB), to test the ability of obtaining CD123 CAR-T from fresh or cryopreserved UCB. We obtained a cell product with a high and stable transduction efficacy, and a poorly differentiated phenotype of CAR-T cells, while retaining high cytotoxic functions in vitro and in vivo. Moreover, CAR-T produced from cryopreserved UCB are as functional as CAR-T produced from fresh UCB. Overall, these data pave the way for the clinical development of UCB-derived CAR-T. UCB CAR-T could be transferred in an autologous manner (after an UCB transplant) to reduce post-transplant relapses, or in an allogeneic setting, thanks to fewer HLA restrictions which ease the requirements for a match between the donor and recipient.

CD123 and More: How to Target the Cell Surface of Blastic Plasmacytoid Dendritic Cell Neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia derived from plasmacytoid dendritic cells (pDCs). It is associated with a remarkably poor prognosis and unmet need for better therapies. Recently, the first-in-class CD123-targeting therapy, tagraxofusp, was approved for treatment of BPDCN. Other CD123-targeting strategies are in development, including bispecific antibodies and combination approaches with tagraxofusp and other novel agents. In other blood cancers, adoptive T-cell therapy using chimeric antigen receptor (CAR)-modified T cells represents a promising new avenue in immunotherapy, showing durable remissions in some relapsed hematologic malignancies. Here, we report on novel and innovative therapies in development to target surface molecules in BPDCN currently in clinical trials or in preclinical stages. We also discuss new cell surface targets that may have implications for future BPDCN treatment.