Abstract 425P
Background
Personalized neoantigen peptide-based therapeutic cancer vaccines, designed to trigger de novo T cell responses against neoantigens, are always considered safe and highly specific to tumours of individual patients, which can amplify and broaden the endogenous repertoire of tumour-specific T cells. However, naked peptide vaccines are often faced with significant challenges such as early enzymatic degradation, poor antigen presentation by dendritic cells (DCs), tumour low immunogenicity, and limited lymph nodes (LNs) trafficking. Therefore, an effective tumour vaccine vector which can rapidly display peptides and promote antigen cross-presentation is urgently needed. Compared with other biomaterials such as Montanide ISA-51 and injectable hydrogels, probiotics which participate in human health dynamically and closely can be utilized as a promising delivery system with the integration of synthetic biology and chemical biotechnology.
Methods
We developed a probiotic food-grade Lactococcus lactis-based in situ vaccination (FOLactis) expressing a fusion protein of Fms-like tyrosine kinase 3 ligand and co-stimulator OX40 ligand, physically attaching neoantigen peptides onto the FOLactis cell wall (Ag-FOLactis) by using a cell penetrating peptide sequence derived from human immunodeficiency virus Tat N-terminally. The in vivo metabolism and biodistribution of Ag-FOLactis was explored using near infrared living imaging. We also checked the neoantigen-reactive T cell response in vivo and ex vivo by flow cytometry.
Results
Ag-FOLactis can keep in the injection site, slow the degradation of peptides and attract DCs to present antigens. In multiple tumour-bearing mouse models, locoregional administration of Ag-FOLactis in lymph nodes significantly triggers tumour-specific T cell response, inhibits tumour growth and prolongs the survival of tumour-bearing mice. Ag-FOLactis also synergizes with an anti-PD1 antibody.
Conclusions
Overall, we find that Ag-FOLactis represents a flexible and powerful personalized cancer vaccine platform for displaying different neoantigen peptides, with enhanced specific anti-tumour immunity and little harm to important organs.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
National Natural Science Foundation of China.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
183P - Final analysis of phase II clinical study evaluating the safety and effectiveness of neoadjuvant S-1 + oxaliplatin combination therapy for older patients with locally advanced gastric cancer
Presenter: Eiji Oki
Session: Poster Display
Resources:
Abstract
184P - Neutropenia as a predictive and prognostic factor in nanoliposomal-irinotecan/fluorouracil/leucovorin therapy for pancreatic cancer: Findings from the NAPOLEON-2 study (NN-2301)
Presenter: Yuki Sonoda
Session: Poster Display
Resources:
Abstract
185P - Disease etiology impact on outcomes of hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab: A real-world, multicenter study
Presenter: Silvia Foti
Session: Poster Display
Resources:
Abstract
186P - Efficacy and safety of fruquintinib with nab-paclitaxel in advanced G/GEJ cancer after exposure to immune checkpoint inhibitors: A single-center prospective clinical trial
Presenter: Xiaoting Ma
Session: Poster Display
Resources:
Abstract
187P - Neoadjuvant cadonilimab (PD-1/CTLA-4 bispecific antibody) plus transhepatic arterial infusion chemotherapy (HAIC) for resectable multinodular CNLC Ib/IIa hepatocellular carcinoma (Car-Hero)
Presenter: Yongguang Wei
Session: Poster Display
Resources:
Abstract
188P - Impact of metformin, statin, aspirin and insulin on the prognosis of unresectable HCC patients receiving first-line lenvatinib or atezolizumab plus bevacizumab
Presenter: Margherita Rimini
Session: Poster Display
Resources:
Abstract
189P - Safety run-in results from LEAP-014: First-line lenvatinib (len) plus pembrolizumab (pembro) and chemotherapy (chemo) for metastatic esophageal squamous cell carcinoma (ESCC)
Presenter: Shun Yamamoto
Session: Poster Display
Resources:
Abstract
190P - Perioperative camrelizumab combined with chemotherapy for locally advanced gastric or gastroesophageal junction adenocarcinoma: A single-arm, single-center, phase II clinical trial
Presenter: Jiaxing He
Session: Poster Display
Resources:
Abstract
191P - Predictive value of CXCR6 expression in gastric cancer survival and immune modulation
Presenter: Song-Hee han
Session: Poster Display
Resources:
Abstract
192P - Antiangiogenesis-related adverse events (ARAE) to predict efficacy in patients with advanced gastric cancer (AGC) treated with apatinib + chemotherapy: Results from two prospective studies
Presenter: Rongbo Lin
Session: Poster Display
Resources:
Abstract