TAS0314, a novel multi-epitope long peptide vaccine, showed synergistic antitumor immunity with PD-1/PD-L1 blockade in HLA-A*2402 mice

Abstract

Cancer peptide vaccines are a promising cancer immunotherapy that can induce cancer-specific cytotoxic T lymphocytes (CTLs) in tumors. However, recent clinical trials of cancer vaccines have revealed that the efficacy of the vaccines is limited. Targeting single antigens and vaccination with short peptides are partly the cause of the poor clinical outcomes. We synthesized a novel multi-epitope long peptide, TAS0314, which induced multiple epitope-specific CTLs in HLA knock-in mice. It also showed superior epitope-specific CTL induction and antitumor activity. We also established a combination treatment model of vaccination with PD-1/PD-L1 blockade in HLA-A*2402 knock-in mice, and it showed a synergistic antitumor effect with TAS0314. Thus, our data indicated that TAS0314 treatment, especially in combination with PD-1/PD-L1 blockade, is a promising therapeutic candidate for cancer immunotherapy.

First‐in‐human study of the cancer peptide vaccine TAS0313 in patients with advanced solid tumors

“…However, PD‐1 Ab treatment is limited for so‐called “cold” tumors, which are poorly infiltrated by CD8 + T cells. Findings from the current study established that TIL induction was generated by treatment with TAS0313 and confirmed similar results observed in previous preclinical studies 27 . Thus, we can postulate that TAS0313 might be effective at converting “cold” tumors to T cell‐infiltrating “hot” tumors, and might have combinatorial efficacy with PD‐1 Abs.…”

“…Findings from the current study established that TIL induction was generated by treatment with TAS0313 and confirmed similar results observed in previous preclinical studies. 27 Thus, we can postulate that TAS0313 might be effective at converting "cold" tumors to T cell-infiltrating "hot" tumors, and might have combinatorial efficacy with PD-1 Abs. However, it is not clear whether this increase was a tumor antigen-specific CTL.…”

Peptide vaccine-treated, long-term surviving cancer patients harbor self-renewing tumor-specific CD8+ T cells

“…In these cases, we observed durable antitumor effects with persistently preserved immune responses by the same TCR clonotypes. However, the CTL induction rates were as low as one-third of the total, which can be improved by the administration of multiple peptides or a combination strategy with PD-1/PD-L1 blockade 26 . We found that an increase in the tetramer + fraction of CD8 + T cells did not always indicate effective CTL induction, possibly because a peptide-MHC complex sometimes binds to a TCR without signal transduction due to inappropriate geometric topology between the two complexes 27 or the dysfunctional phenotype of CD8 T cells that fail to produce inflammatory cytokines upon antigen stimulation 28 .…”

Development of Peptide-Based Vaccines for Cancer

“…Recently, the study by Tanaka et al utilizing a novel multiepitope long peptide vaccine, TAS0314, demonstrated a synergistic antitumor immunity in combination treatment with PD-1/PD-L1 blockade in HLA-A ∗ 2402 knock-in mice [ 145 ]. The combination of TAS0314 plus anti-PD-1 antibody dramatically reduced tumor development and prolonged survival when compared to monotherapy alone.…”