Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patientsReport as inadecuate




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Journal of Translational Medicine

, 12:84

Clinical translation

Abstract

BackgroundChemoradiation therapy CRT has been widely used for unresectable esophageal squamous cell carcinoma ESCC patients. However, many patients develop local recurrence after CRT. In this study, we hypothesized that the immunotherapy by peptide vaccine may be effective for the eradication of minimal residual cancer cells after CRT. This study was conducted as a phase I clinical trial of multiple-peptide vaccine therapy combined with CRT on patients with unresectable ESCC.

Patients and methodsHLA-A*2402 positive 11 unresectable chemo-naïve ESCC patients were treated by HLA-A*2402-restricted multi-peptide vaccine combined with CRT. The peptide vaccine included the 5 peptides as follows; TTK protein kinase TTK, up-regulated lung cancer 10 URLC10, insulin-like growth factor–II mRNA binding protein 3 KOC1, vascular endothelial growth factor receptor 1 VEGFR1 and 2 VEGFR2. CRT consisted of radiotherapy 60 Gy with concurrent cisplatin 40 mg-m and 5-fluorouracil 400 mg-m. Peptide vaccines mixed with incomplete Freund’s adjuvant were injected subcutaneously once a week on at least 8 occasions combined with CRT.

ResultsVaccination with CRT therapy was well-tolerated, and no severe adverse effects were observed. In the case of grade 3 toxicities, leucopenia, neutropenia, anemia and thrombocutopenia occurred in 54.5%, 27.3%, 27.3% and 9.1% of patients, respectively. Grade 1 local skin reactions in the injection sites of vaccination were observed in 81.8% of patients. The expressions of HLA class I, URLC10, TTK, KOC1, VEGFR1 and VEGFR2 antigens were observed in the tumor tissues of all patients. All patients showed peptide-specific cytotoxic T lymphocytes responses in at least one of the 5 kinds of peptide antigens during the vaccination. Six cases of complete response CR and 5 cases of progressive disease PD were observed after the 8 vaccination. The 4 CR patients who continued the peptide vaccination experienced long consistent CR for 2.0, 2.9 4.5 and 4.6 years.

ConclusionsA combination therapy of multi-peptide vaccine with CRT can successfully be performed with satisfactory levels of safety, and application of this combination therapy may be an effective treatment for patients with unresectable ESCC.

Trial registrationClinicalTrial.gov, number NCT00632333.

KeywordsCancer vaccine Chemoradiation therapy Esophageal cancer CTL Phase I clinical trial AbbreviationsESCCEsophageal squamous cell carcinoma

CRTChemoradiation therapy

TTKTTK protein kinase

URLC10Up-regulated lung cancer 10

KOC1Insulin-like growth factor–II mRNA binding protein 3

VEGFR1Vascular endothelial growth factor receptor 1

VEGFR2Vascular endothelial growth factor receptor 2

ELISPOTEnzyme-linked immunospot

PBMCPeripheral blood mononuclear cells

CTLCytotoxic T lymphocytes

CRComplete clinical response

PDProgressive disease

IHCImmunohistochemical

PFSProgression free survival.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-12-84 contains supplementary material, which is available to authorized users.

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Author: Hisae Iinuma - Ryoji Fukushima - Tsuyoshi Inaba - Junko Tamura - Taisuke Inoue - Etsushi Ogawa - Masahiro Horikawa - Yoshib

Source: https://link.springer.com/







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