Data from Neoadjuvant BO-112 and Hypofractionated Radiation Therapy with or without Nivolumab in Soft-Tissue Sarcoma: Preclinical and Phase I Results

作者：Jie Deng, Aastha Pal, Stefano Testa, Jingyu W. Xu, Linh M. Tran, Danielle S. Graham, Aviv Hargill, Ajay Subramanian, Katie M. Campbell, Sam P. Limsuwannarot, Alvaro Chumpitaz Lavalle, Scott Chin, Sarah Kremer, Mito Tariveranmoshabad, Agnes Ewongwo, S. K. Nadia Rahman Silvia, Heather Ogana, Neda Nemat‐Gorgani, Steven M. Dubinett, Jillian R. Jaycox, Carol Felix, Dörthe Schaue, Scott D. Nelson, Benjamin D. Levine, Kambiz Motamedi, Varand Ghazikhanian, Bartosz Chmielowski, Vishruth K. Reddy, Arun S. Singh, Zuzana Jiráková Trnková, Zinaida Good, Marisol Quintero, Joseph G. Crompton, Nicholas M. Bernthal, Fritz C. Eilber, Everett J. Moding, Anusha Kalbasi · 年份：2026 · DOI：10.1158/2159-8290.c.8568787 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、CAR-T cell therapy research

<div>Abstract<p>Neoadjuvant immune checkpoint blockade (ICB) and radiotherapy (RT) improve disease-free survival in select patients with soft-tissue sarcoma (STS). However, most STS are myeloid-rich and lack preexisting T cells associated with ICB response. In preclinical models, we observed that intratumoral BO-112 [nanoplexed polyinosinic: polycytidylic acid (poly I:C)] engages myeloid cells that persist after RT, ultimately enhancing T cell–dependent tumor control. We evaluated BO-112 and hypofractionated RT, with or without nivolumab, in 14 patients with high-risk STS in a phase I neoadjuvant trial. Consistent with its immunologic potency, the triple combination induced rare immune-related adverse events (myositis–myocarditis–myasthenia gravis spectrum), mitigated by BO-112 and nivolumab dose adjustment. BO-112 and RT reprogrammed tumor-associated myeloid cells toward antigen-presenting states, promoted clonal replacement by less exhausted T cells, and enhanced malignant cell depletion compared with standard RT. These immunologic changes coincided with encouraging disease control in a small, high-risk cohort, supporting further clinical development.</p>Significance:<p>Intratumoral BO-112 and hypofractionated RT activate systemic T-cell immunity in mouse models and in a phase I neoadjuvant study of high-risk, resectable sarcoma. Engaging myeloid cells with BO-112 represents a potent strategy with RT to replete T cell–deficient tumors and expand the ...