Multicenter, phase II clinical trial of peptide vaccination with oral chemotherapy following curative resection for stageï¿½III colorectal cancer

Kawamura, Junichiro; Sugiura, Fumiaki; Sukegawa, Yasushi; Yoshioka, Yasumasa; Hida, Jin‐ichi; Hazama, Shoichi; Okuno, Kiyotaka

doi:10.3892/etm.2018.5802

Cited by 3 publications

(4 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Approximately 70% of the patients in this trial showed specific CTL induction to each of the peptides. This finding is superior to those of previous reports [ 3 – 5 , 32 ]. Additionally, patients receiving dose level 3 (1.0 mg hLAG-3Ig + 1.4 mg Poly-ICLC/injection) had significantly faster and stronger peptide-specific CTL induction than those at dose levels 1 and 2.…”

Section: Discussioncontrasting

confidence: 95%

A phase I study of multi-HLA-binding peptides derived from heat shock protein 70/glypican-3 and a novel combination adjuvant of hLAG-3Ig and Poly-ICLC for patients with metastatic gastrointestinal cancers: YNP01 trial

Nakajima

Hazama

Tamada

et al. 2020

Cancer Immunol Immunother

Self Cite

View full text Add to dashboard Cite

Background This phase I study aimed to evaluate the safety, peptide-specific immune responses, and anti-tumor effects of a novel vaccination therapy comprising multi-HLA-binding heat shock protein (HSP) 70/glypican-3 (GPC3) peptides and a novel adjuvant combination of hLAG-3Ig and Poly-ICLC against metastatic gastrointestinal cancers. Methods HSP70/GPC3 peptides with high binding affinities for three HLA types (A*24:02, A*02:01, and A*02:06) were identified with our peptide prediction system. The peptides were intradermally administered with combined adjuvants on a weekly basis. This study was a phase I dose escalation clinical trial, which was carried out in a three patients’ cohort; in total, 11 patients were enrolled for the recommended dose. Results Seventeen patients received this vaccination therapy without dose-limiting toxicity. All treatment-related adverse events were of grades 1 to 2. Peptide-specific CTL induction by HSP70 and GPC3 proteins was observed in 11 (64.7%) and 13 (76.5%) cases, respectively, regardless of the HLA type. Serum tumor marker levels were decreased in 10 cases (58.8%). Immunological analysis using PBMCs indicated that patients receiving dose level 3 presented with significantly reduced T cell immunoglobulin and mucin-domain containing-3 (TIM3)-expressing CD4 + T cells after one course of treatment. PD-1 or TIM3-expressing CD4 + T cells and T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT)-expressing CD8 + T cells in PBMCs before vaccination were negative predictive factors for survival. Conclusions This novel peptide vaccination therapy was safe for patients with metastatic gastrointestinal cancers. Electronic supplementary material The online version of this article (10.1007/s00262-020-02518-7) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussioncontrasting

confidence: 95%

A phase I study of multi-HLA-binding peptides derived from heat shock protein 70/glypican-3 and a novel combination adjuvant of hLAG-3Ig and Poly-ICLC for patients with metastatic gastrointestinal cancers: YNP01 trial

Nakajima

Hazama

Tamada

et al. 2020

Cancer Immunol Immunother

Self Cite

View full text Add to dashboard Cite

show abstract

“…Detailed information of the study design was described previously . Briefly, this was a phase II, non‐randomized, single‐arm study in which the HLA‐A status was double‐blinded.…”

Section: Methodsmentioning

confidence: 99%

“…We previously reported a phase I clinical trial of a peptide vaccine ring finger protein 43 (RNF43) and 34‐kDa translocase of the outer mitochondrial membrane (TOMM34) combined with uracil‐tegafur (UFT)/LV for patients with metastatic CRC, and demonstrated the safety and immunological responsiveness of this combination therapy . In this study, we evaluated vaccination‐induced immune responses to clarify the survival benefit of a peptide vaccine combined with UFT/LV as adjuvant treatment for selected patients with stage III CRC.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage III colorectal cancer

et al. 2018

Self Cite

View full text Add to dashboard Cite

We previously reported a phase I clinical trial of a peptide vaccine ring finger protein 43 (RNF43) and 34‐kDa translocase of the outer mitochondrial membrane (TOMM34) combined with uracil‐tegafur (UFT)/LV for patients with metastatic colorectal cancer (CRC), and demonstrated the safety and immunological responsiveness of this combination therapy. In this study, we evaluated vaccination‐induced immune responses to clarify the survival benefit of the combination therapy as adjuvant treatment. We enrolled 44 patients initially in an HLA‐masked fashion. After the disclosure of HLA, 28 patients were in the HLA‐A*2402‐matched and 16 were in the unmatched group. In the HLA‐matched group, 14 patients had positive CTL responses specific for the RNF43 and/or TOMM34 peptides after 2 cycles of treatment and 9 had negative responses; in the HLA‐unmatched group, 10 CTL responses were positive and 2 negative. In the HLA‐matched group, 3‐year relapse‐free survival (RFS) was significantly better in the positive CTL subgroup than in the negative‐response subgroup. Patients with negative vaccination‐induced CTL responses showed a significant trend towards shorter RFS than those with positive responses. Moreover, in the HLA‐unmatched group, the positive CTL response subgroup showed an equally good 3‐year RFS as in the HLA‐matched group. In conclusion, vaccination‐induced CTL response to peptide vaccination could predict survival in the adjuvant setting for stage III CRC.

show abstract

“…DC-based vaccines have been included in trials on CCA, whereas a phase II study was conducted in the adjuvant setting in order to target mucin 1 (MUC1) in the biliary tract and in PC via DC vaccination, and the tolerability was reported to be good, although it was not possible to draw definitive conclusions regarding the immune response (54). Further phase II clinical trials involving CRC-specific peptide vaccines were performed with patients diagnosed with HLA-A*2402-positive stage III CRC, with the findings suggesting that an immune response would be generated by the vaccine, leading to higher survival rates (55). For patients with PC, 13-mer mutant ras peptide vaccines were not only shown to be safe, but to also generate the appropriate immune response (56).…”

Section: Vaccine Therapy In Gi Cancersmentioning

confidence: 99%

The role of immunogenic cell death in gastrointestinal cancer immunotherapy (Review)

et al. 2021

View full text Add to dashboard Cite

Modern cancer immunotherapy techniques are aimed at enhancing the responses of the patients' immune systems to fight against the cancer. The main promising strategies include active vaccination of tumor antigens, passive vaccination with antibodies specific to cancer antigens, adoptive transfer of cancer-specific T cells and manipulation of the patient's immune response by inhibiting immune checkpoints. The application of immunogenic cell death (ICD) inducers has been proven to enhance the immunity of patients undergoing various types of immunotherapy. The dying, stressed or injured cells release or present molecules on the cell surface, which function as either adjuvants or danger signals for detection by the innate immune system. These molecules are now termed ‘damage-associated molecular patterns’. The term ‘ICD’ indicates a type of cell death that triggers an immune response against dead-cell antigens, particularly those derived from cancer cells, and it was initially proposed with regards to the effects of anticancer chemotherapy with conventional cytotoxic drugs. The aim of the present study was to review and discuss the role and mechanisms of ICD as a promising combined immunotherapy for gastrointestinal tumors.

show abstract

Multicenter, phase II clinical trial of peptide vaccination with oral chemotherapy following curative resection for stageï¿½III colorectal cancer

Cited by 3 publications

References 0 publications

A phase I study of multi-HLA-binding peptides derived from heat shock protein 70/glypican-3 and a novel combination adjuvant of hLAG-3Ig and Poly-ICLC for patients with metastatic gastrointestinal cancers: YNP01 trial

A phase I study of multi-HLA-binding peptides derived from heat shock protein 70/glypican-3 and a novel combination adjuvant of hLAG-3Ig and Poly-ICLC for patients with metastatic gastrointestinal cancers: YNP01 trial

Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage III colorectal cancer

The role of immunogenic cell death in gastrointestinal cancer immunotherapy (Review)

Contact Info

Product

Resources

About