Intranodal injection of neoantigen-bearing engineered Lactococcus lactis triggers epitope spreading and systemic tumor regressions.
10.1016/j.apsb.2025.02.041
- Author:
Junmeng ZHU
1
;
Yi SUN
1
;
Xiaoping QIAN
1
;
Lin LI
2
;
Fangcen LIU
3
;
Xiaonan WANG
1
;
Yaohua KE
1
;
Jie SHAO
4
;
Lijing ZHU
1
;
Lifeng WANG
1
;
Qin LIU
1
;
Baorui LIU
1
Author Information
1. The Comprehensive Cancer Centre, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China.
2. Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing 210008, China.
3. Department of Pathology, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.
4. The Clinical Cancer Institute of Nanjing University, Nanjing 210008, China.
- Publication Type:Journal Article
- Keywords:
Cancer vaccine;
Cell-penetrating peptide;
Epitope spreading;
Intranodal injection;
Neoantigen;
Probiotic;
Synthetic biology;
Tumor immunology
- From:
Acta Pharmaceutica Sinica B
2025;15(4):2217-2236
- CountryChina
- Language:English
-
Abstract:
Probiotics are natural systems bridging synthetic biology, physical biotechnology, and immunology, initiating innate and adaptive anti-tumor immune activity. We previously constructed an all-in-one engineered food-grade probiotic Lactococcus lactis (FOLactis) which could boost the crosstalk among different immune cells such as dendritic cells (DCs), natural killer cells, and T cells. Herein, considering the limited clinical efficacy of naked personalized neoantigen peptide vaccines, we decorate FOLactis with tumor antigens by employing a Plug-and-Display system comprising membrane-inserted peptides. Intranodal injection of FOLactis coated with neoantigen peptides (Ag-FOLactis) induces robust DCs presentation and neoantigen-specific cellular immunity. Notably, Ag-FOLactis not only triggers a 45-fold rise in the quantity of locally reactive neoantigen-specific T cells but also induces epitope spreading in both subcutaneous and metastatic tumor-bearing models, leading to potent inhibition of tumor growth. These findings imply that Ag-FOLactis represents a powerful platform to rapidly and easily display antigens, facilitating the development of a bio-activated platform for personalized therapy.
