An Immunomodulator‐Boosted Lactococcus Lactis Platform For Enhanced In Situ Tumor Vaccine

In situ vaccination is an attractive type of cancer immunotherapy, and methods of persistently dispersing immune agonists throughout the entire tumor are crucial for maximizing their therapeutic efficacy. Based on the probiotics usually used for dietary supplements, an immunomodulator‐boosted Lactococcus lactis (IBL) strategy is developed to enhance the effectiveness of in situ vaccination with the immunomodulators. The intratumoral delivery of OX40 agonist and resiquimod‐modified Lactococcus lactis (OR@Lac) facilitates local retention and persistent dispersion of immunomodulators, and dramatically modulates the key components of anti‐tumor immune response. This novel vaccine activated dendritic cells and cytotoxic T lymphocytes in the tumor and tumor‐draining lymph nodes, and ultimately significantly inhibited tumor growth and prolonged the survival rate of tumor‐bearing mice. The combination of OR@Lac and ibrutinib, a myeloid‐derived suppressor cell inhibitor, significantly alleviated or even completely inhibited tumor growth in tumor‐bearing mice. In conclusion, IBL is a promising in situ tumor vaccine approach for clinical application and provides an inspiration for the delivery of other drugs. An innovative in situ vaccine strategy that αOX40 and resiquimod (R848) are modified to the surface of L. lactis, resulting in the generation of dual immune adjuvant modified L. lactis (OR@Lac) are presented. Then, OR@Lac in combination with ibrutinib significantly alleviated or even completely inhibited tumor growth in tumor‐bearing mice.