Abstract 6331: The anti-tumor activity of HSP-90 therapeutic cancer vaccine (AST-021p) combine with TLR2/3 agonist in a MMTV-neu transgenic model

• Published in: Cancer research (Chicago, Ill.) Ill.), 2023-04, Vol.83 (7_Supplement), p.6331-6331
• Main Authors: Kang, JinHo, Choi, Jee Hyun, Seo, Min Ji, Jung, Eunjung, Ahn, Byung cheol, Lim, Jinback, Park, Hyo-Hyun, Shin, Hyunwon, Joung, Eunkyo, Jung, Hun, Park, Kyong Hwa
• Format: Article
• Language: English
• ISSN: 1538-7445; 1538-7445
• DOI: 10.1158/1538-7445.AM2023-6331

Background: AST-021p, which is derived from HLA class II binding epitopes of human HSP90 protein, is an investigational therapeutic cancer vaccine for the malignant neoplasms. AST-021p is designed to demonstrate the immunologic efficacy by activating antigen-specific CD4+ Th1 cell in humans. Due to their ability to link the innate with the adaptive immune response, Toll-like receptor (TLR) agonists are highly promising as adjuvants in vaccines against life-threatening and complex diseases such as cancer, AIDS and malaria. In this study, AST-021p was investigated to evaluate the immunogenicity and tumor growth inhibitory effect under the condition of combining with various immune adjuvants derived from TLR agonists, using in-vivo model. Methods: Three different agonists of TLR (TLR-4, TLR-2/3, TLR-7/8) were assigned to investigate the immunogenicity in each group (4 FVB/N mice/group, total 4 groups). AST-021p was intradermally injected 3 times with different TLR-agonists and the immunogenicity was assessed from mouse splenocyte by HSP90-specific IFN-γ ELISpot method. We also examined the efficacy of AST-021p and selected TLR-agonist in MMTV/neu Tg mice (4 mice/group, conducted twice and A total 8 mice was assigned to each group). The combination of AST-021p and TLR-2/3 agonist (AST-021p plus TLR-2/3 agonist) was injected 3 times every 10 days to mice followed by inoculated mouse mammary cancer cell line. The tumor volume change and immunogenicity were evaluated. Results: The most effective TLR-agonist as a potent immune adjuvant was a TLR-2/3 agonist (L-pampoTM, supplied by CHA Vaccine Institute). AST-021p (100 μg) plus TLR-2/3 agonist significantly improved immunogenicity by increasing HSP-90 epitope-specific T cells up to 130±10 per 1x105 spleen cell of FVB/N mice (P