Oncolytic virotherapy harnesses genetically engineered viruses to selectively infect and lyse tumor cells while stimulating antitumor immunity through pro-inflammatory microenvironment activation. Celyvir represents a pioneering cell-based oncolytic therapy combining mesenchymal stromal cells (MSCs) as carriers of the human oncolytic adenovirus ICOVIR-5. Developed over two decades through collaborative efforts, Celyvir leverages the tumor-homing capacity of MSCs to enhance systemic delivery and therapeutic efficacy of oncolytic virotherapy against solid tumors. Preclinical and clinical studies, including compassionate use programs and phase I trials, have demonstrated Celyvir's safety, feasibility, and potential efficacy. Mechanistic insights reveal that MSCs with a low pro-inflammatory profile and patients' baseline immune competence correlate with improved responses. The evolution from autologous (Celyvir) to allogeneic MSC-based delivery (AloCelyvir) aims to overcome manufacturing delays and optimize clinical outcomes. This review summarizes the conceptual foundations, preclinical models, translational milestones, and ongoing clinical trials of Celyvir, illustrating its trajectory from bench to bedside as an improved oncolytic virotherapy modality.
Morales-Molina et al. (Wed,) studied this question.