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
203P - Neoadjuvant durvalumab plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (ESCC)
Presenter: Jia He
Session: Poster Display
Resources:
Abstract
204P - A radiomics strategy based on CT intra-tumoral and peritumoral regions for preoperative prediction of neoadjuvant chemoradiotherapy for esophageal cancer
Presenter: zhiyang li
Session: Poster Display
Resources:
Abstract
205TiP - IMPACT: Randomized, multicenter, phase III study evaluating the efficacy of immunotherapy (atezolizumab) plus anti-VEGF therapy (bevacizumab) in combination with transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma (HCC)
Presenter: Tatsuya Yamashita
Session: Poster Display
Resources:
Abstract
206TiP - SIERRA: A phase IIIb, single-arm, multicentre study of tremelimumab plus durvalumab for first-line treatment of advanced unresectable hepatocellular carcinoma
Presenter: Stephen Chan
Session: Poster Display
Resources:
Abstract
207TiP - A two-arm randomized open-label prospective design superiority phase III clinical trial to compare the efficacy of docetaxel-oxaliplatin-capecitabine/ 5 -fluorouracil (DOC/F) followed by docetaxel versus CAPOX/mFOLFOX-7 in advanced gastric cancers
Presenter: Prabhat Bhargava
Session: Poster Display
Resources:
Abstract
212P - Mutational landscape and characteristics of ERBB2 in urothelial carcinoma
Presenter: Mingwei Li
Session: Poster Display
Resources:
Abstract
213P - Prognostic significance of absolute lymphocyte count in patients with metastatic renal cell carcinoma treated with first-line combination immunotherapies: Results from the International metastatic renal cell carcinoma database consortium (IMDC)
Presenter: Kosuke Takemura
Session: Poster Display
Resources:
Abstract
214P - Development and prospective validation of a multiplex RNA urine test for noninvasive detection and surveillance of urothelial carcinoma
Presenter: Hua Xu
Session: Poster Display
Resources:
Abstract
215P - Real-world outcomes of first-line tislelizumab plus axitinib in patients with metastatic non-clear cell renal cell carcinoma (mnccRCC)
Presenter: Pei Dong
Session: Poster Display
Resources:
Abstract
216P - Preliminary efficacy and safety results from ‘ReBirth’: A phase II study of risk-based bladder-sparing therapy for MIBC
Presenter: Yijun Shen
Session: Poster Display
Resources:
Abstract