Neoadjuvant intratumoral MBT(A) immunotherapy prevents distant metastases and recurrence in murine models.

Neoadjuvant immunotherapy represents a pioneering approach in the preoperative treatment of cancer, providing new strategies for tumor reduction and improved patient outcomes by modulating the immune response. This study investigated neoadjuvant immunotherapy using intratumoral administration of mannan-BAM, Toll-like receptor ligands, and anti-CD40 antibody (MBTA therapy) followed by surgery in murine models of MTT pheochromocytoma, B16-F10 melanoma, and 4T1 and E0771.lmb mammary carcinomas. In the MTT pheochromocytoma model, it was found that neoadjuvant MBTA therapy followed by surgery could prevent the development of distant metastases in 100% of treated animals, compared to a 60% mortality rate in the control group due to metastatic disease after surgery. These outcomes were achieved even in tumors three times larger than those in the control group. In the aggressive 4T1 model, neoadjuvant MBTA therapy resulted in slower tumor progression and a significant prolongation of survival. In the B16-F10 and E0771.lmb models, neoadjuvant MBTA therapy also protected animals from metastases development and tumor recurrence upon rechallenge with tumor cells after surgery. Transcriptomic analysis revealed enhanced effector immune cell infiltration, cytotoxicity, and antigen presentation in retransplanted tumors from MBTA-treated mice, indicating robust immune memory. Notably, the exclusion of the anti-CD40 antibody from the neoadjuvant MBTA therapy (MBT therapy) yielded comparable outcomes in protection against metastases development. These findings advocate for further investigation of intratumoral neoadjuvant MBTA therapy for immunologically "cold" tumors, including those at high risk of metastases or recurrence.