Abstract 489P
Background
Engineered bacteria have demonstrated significant promise in cancer immunotherapy by continuously releasing therapeutic agents and promoting a sustained antitumor immune response through interactions with immune cells. We previously designed an all-in-one engineered food-grade probiotic Lactococcus lactis (FOLactis). Given the limited clinical efficacy of naked personalized neoantigen peptide vaccines, we decorated FOLactis with tumor antigens using a Plug-and-Display system that incorporates membrane-inserted peptides. Intranodal injection of FOLactis coated with neoantigen peptides (AgFOLactis) induces robust DCs presentation and neoantigen-specific cellular immunity in various metastatic tumor models.
Methods
We previously engineered a probiotic Lactococcus lactis (FOLactis) expressing a fusion protein of Fms-like tyrosine kinase 3 and co-stimulator OX40 ligands. Then we opted for a cell-penetrating peptide (CPP) sequence and conjugated it to the N terminus of the therapeutic neoantigen peptides. Ag-FOLactis was constructed by co-incubating FOLactis with the peptides. Ag-FOLactis were characterized in vitro using flow cytometry, confocal microscopy and transmission electron microscopy (TEM). The antitumor effect of the Ag-FOLactis platform in vivo was assessed in lung melanoma metastasis mouse models, as well as in peritoneal metastasis mouse models.
Results
The suppression of tumor progression by Ag-FOLactis was markedly more pronounced in contrast to the other groups. We focused on the immune function of mouse splenocytes to investigate the mechanism behind the anti-tumor effect elicited by the vaccine. Compared with naked CPP-peptide, Ag-FOLactis induced a significant increase of CD3+ CD8+ T cells, IFN-γ-secreting CD3+ CD8+ T cells, and effector memory T cells (TEM), with a slight decrease in the proportion of central memory T cells (TCM). Programmed death 1 blockade antibody combination further enhances the antitumor efficacy of Ag-FOLactis.
Conclusions
To conclude, it is worth to apply Ag-FOLactis in different metastatic tumor-bearing mouse models, which highlights the tremendous clinical translational value of this vaccine platform.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
B. Liu.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.