Abstract 34P
Background
Cancer stem cells (CSCs) account for the resistance to chemo/radiotherapies and the cancer-initiating abilities of low numbers of cells in vivo. CSCs significantly contribute to cancer recurrence and metastasis, presenting a formidable challenge to oral cancer prognosis. While targeting CSCs with a peptide vaccine has demonstrated greater efficacy, the use of a singular peptide vaccine may pose a risk of immune evasion. Our objective was to develop an innovative cocktail peptide vaccine by combining multiple peptides to effectively target CSCs.
Methods
The well-established CSC marker CD44 facilitated the isolation of oral CSCs. CD44-positive cell groups exhibited elevated CSC markers, enhanced sphere-forming ability, and heightened resistance to chemotherapy and radiation therapy, confirming CSC properties. We searched for genes enriched in oral CSCs and investigated whether cytotoxic T lymphocytes (CTLs) induced by peptides from these genes demonstrated effective cytotoxicity.
Results
Comparative gene expression showed elevated levels of oral CSCs compared to non-CSCs for OR7C1, an olfactory receptor involved in odorant detection, and a colorectal CSC gene, CLSPN, a key regulator in the DNA replication checkpoint pathway for precise cell cycle progression. Stimulation of donor PBMCs with an HLA-A24-restricted OR7C1 peptide induced OR7C1-specific CTLs, targeting and damaging cancer cells expressing HLA-A24 and OR7C1. Similarly, an HLA-A2-restricted CLSPN peptide induced CLSPN-specific CTLs, targeting and damaging cancer cells expressing HLA-A2 and CLSPN. The Survivin 2B peptide, already applied clinically, induced specific CTLs and damaged cancer cells expressing HLA-A24 and Survivin 2B. Survivin 2B gene expression was comparable in both CSC and non-CSC populations.
Conclusions
OR7C1 and CLSPN peptides induced CSC-specific CTLs. Survivin 2B peptide exhibited reactivity against both CSC and non-CSC populations. A more effective therapeutic outcome is proposed with personalized, HLA-tailored cocktail vaccines, promising advancements in oral cancer treatment strategies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Japan Society for the Promotion of Science.
Disclosure
All authors have declared no conflicts of interest.