Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, China.
Department of Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
Adv Healthc Mater. 2024 Nov;13(28):e2401635. doi: 10.1002/adhm.202401635. Epub 2024 Jul 25.
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.
原位疫苗接种是一种有吸引力的癌症免疫疗法，而持续将免疫激动剂分散到整个肿瘤中的方法对于最大限度地提高其治疗效果至关重要。基于通常用于膳食补充剂的益生菌，开发了一种免疫调节剂增强的乳球菌（IBL）策略，以增强免疫调节剂的原位疫苗接种的有效性。OX40 激动剂和瑞喹莫德修饰的乳球菌（OR@Lac）的瘤内递送有助于免疫调节剂的局部保留和持续分散，并显著调节抗肿瘤免疫反应的关键组成部分。这种新型疫苗在肿瘤和肿瘤引流淋巴结中激活了树突状细胞和细胞毒性 T 淋巴细胞，最终显著抑制了肿瘤生长并延长了荷瘤小鼠的存活率。OR@Lac 与髓源抑制细胞抑制剂伊布替尼的联合使用，显著减轻甚至完全抑制了荷瘤小鼠的肿瘤生长。总之，IBL 是一种有前途的临床应用的原位肿瘤疫苗方法，为其他药物的递送提供了启示。
