QUAIL-100 Induces Distinct, Multifunctional Gamma Delta T Cell Responses with Enhanced Durability Compared to Zoledronic Acid in Post-HSCT Pediatric Leukemia Patients
Gamma Delta T cells mediate potent anti-leukemic and anti-infective immunity followingallogeneic hematopoietic stem cell transplantation (HSCT); however, standard VGamma9 VDelta2 activation with zoledronic acid (ZOL) induces rapid terminal differentiation and functional exhaustion, limiting sustained therapeutic efficacy. Pathogen-driven Gamma Delta T cell responses, including those elicited by cytomegalovirus (CMV), exhibit greater functional diversity and durability, providing a conceptual framework for multimodal activation strategies. QUAIL-100, a quadruple-attenuated Listeria monocytogenes strain, was evaluated as a novel Gamma Delta T cell activator that engages combinatorial signals including phosphoantigens, pathogen-associated molecular patterns, and co-stimulatory pathways.