Identification of Lck-derived peptides capable of inducing HLA-A2-restricted and tumor-specific CTLs in cancer patients with distant metastases

Imai, Nobue; Harashima, Nanae; Ito, Masaaki; Miyagi, Yoshiaki; Harada, Mamoru; Yamada, Akira; Itoh, Kyogo

doi:10.1002/ijc.1461

Cited by 35 publications

(26 citation statements)

References 30 publications

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“…Although the repertoire of peptide speciWcity of TIL-derived T cell clones was wide (Table 3), including almost each of the diVerent GCAA peptides tested, those speciWc for peptides belonging to SART3 and lck cancer antigens were the majority, being 24 and 32, respectively. For this aspect, our results are in agrement with the data of previous studies, which reported that the host immune response to gastric cancer frequently target SART and lck tumor-associatedantigens [16,26,33,36].…”

Section: Discussionsupporting

confidence: 90%

Characterization of tumor antigen peptide-specific T cells isolated from the neoplastic tissue of patients with gastric adenocarcinoma

Amedei

Niccolai

Bella

et al. 2009

Cancer Immunol Immunother

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Gastric cancer is a signiWcant cause of morbidity and mortality worldwide. Surgical resection remains the primary curative treatment for gastric adenocarcinoma, but the poor (15-35%) survival rate at 5 years has prompted many studies for new therapeutic strategies, such as speciWc immunotherapy. The aim of this study was to analyze the functional properties of the T cell response to diVerent antigen peptides related to gastric cancer in patients with gastric adenocarcinoma. To this purpose, we have cloned and characterized tumor-inWltrating T cells (TILs) isolated from the neoplastic gastric tissue samples. A T cell response speciWc to diVerent peptides of gastric cancer antigens tested was documented in 17 out of 20 patients, selected for their HLA-A02 and/or -A24 alleles. Most of the cancer peptidespeciWc TILs expressed a Th1/Tc1 proWle and cytotoxic activity against target cells. The eVector functions of cancer peptide-speciWc T cells obtained from the peripheral blood of the same patients were also studied. The majority of peripheral blood peptide-speciWc T cells also expressed the Th1/Tc1 functional proWle. In conclusion, in most of the patients with gastric adenocarcinoma, a speciWc type-1 T cell response to gastric cancer antigens was detectable and would have the potential of hamper tumor cell growth. However, in order to get tumor cell killing in vivo, the activity and the number of cancer peptide-speciWc Th1/Tc1 cells probably need to be enhanced by vaccination with the appropriate cancer antigenic peptides or by injection of the autologus tumor peptide-speciWc T cells expanded in vitro.

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Section: Discussionsupporting

confidence: 90%

Characterization of tumor antigen peptide-specific T cells isolated from the neoplastic tissue of patients with gastric adenocarcinoma

Amedei

Niccolai

Bella

et al. 2009

Cancer Immunol Immunother

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“…In combination with known Lck peptides for HLA-A2 þ or -A24 þ cancer patients Imai et al, 2001), those identified in the present study enable us to develop a peptidebased anti-cancer vaccine for cancer patients with metastases in diverse ethnic populations. % lysis * Figure 4 Peptide-specific cytotoxicity against cancer cells.…”

Section: Discussionmentioning

confidence: 91%

“…We previously reported that HLA-A24-restricted tumourreactive CTLs from patients with distant metastases can recognise Lck-derived peptides as a tumour antigen . We also identified Lck-derived peptides that were applicable to metastatic cancer patients positive for HLA-A2 molecules (Imai et al, 2001). Thereafter, we carried out peptide-based immunotherapy against various types of cancer in which Lck-derived peptides were vaccinated into HLA-A24 þ or -A2 þ cancer patients (Sato et al, 2003;Mine et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Identification of Lck-derived peptides applicable to anti-cancer vaccine for patients with human leukocyte antigen-A3 supertype alleles

et al. 2007

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The identification of peptide vaccine candidates to date has been focused on human leukocyte antigen (HLA)-A2 and -A24 alleles. In this study, we attempted to identify cytotoxic T lymphocyte (CTL)-directed Lck-derived peptides applicable to HLA-þ cancer patients, because these HLA-A alleles share binding motifs, designated HLA-A3 supertype alleles, and because the Lck is preferentially expressed in metastatic cancer. Twenty-one Lck-derived peptides were prepared based on the binding motif to the HLA-A3 supertype alleles. They were first screened for their recognisability by immunoglobulin G (IgG) in the plasma of prostate cancer patients, and the selected candidates were subsequently tested for their potential to induce peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A3 supertype þ cancer patients. As a result, four Lck peptides were frequently recognised by IgGs, and three of them -Lck 90À99 , Lck 449À458 , and Lck 450À458 -efficiently induced peptide-specific and cancerreactive CTLs. Their cytotoxicity towards cancer cells was mainly ascribed to HLA class I-restricted and peptide-specific CD8 þ T cells. These results indicate that these three Lck peptides are applicable to HLA-A3 supertype þ cancer patients, especially those with metastasis. This information could facilitate the development of peptide-based anti-cancer vaccine for patients with alleles other than HLA-A2 and -A24.

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“…This patient received vaccination of the SART3 302-310, Lck 246-254, WHS 103-111 and HNR 140-148 peptides, and we have already reported that all of these peptides can be presented by HLA-A*0206 molecules. (22)(23)(24) We next examined whether or not personalized peptide vaccination in combination with TS-1 could augment peptide-specific CTL or IgG in patients after the sixth vaccination ( Table 1). The vaccination increased peptide-specific CTL response to two, three and one of the four vaccinated peptides in patients 1, 2 and 3, respectively, who had no CTL activity in prevaccination PBMC and received the vaccination combined with a maximum dose (80 mg/m 2 /day) of TS-1.…”

Section: Methodsmentioning

confidence: 99%

Immunological evaluation of personalized peptide vaccination in combination with a 5‐fluorouracil derivative (TS‐1) for advanced gastric or colorectal carcinoma patients

et al. 2007

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The aim of the present study was to investigate the safety and immunological responses of personalized peptide vaccination in combination with oral administration of a 5-fluorouracil derivative (TS-1) in advanced gastric or colorectal carcinoma patients. Eleven patients (four with gastric cancer and seven with colorectal cancer) who failed to improve by prior TS-1-based chemotherapies were enrolled in this study. Peptides to be administered to patients were determined based on the presence of peptide-specific cytotoxic T lymphocyte ( (1) Cancer vaccines have emerged as a promising therapeutic approach, (2) but their clinical responses have been limited.(3) In order to develop a new treatment modality, we recently devised a new regime of peptide-based vaccination that consists of measuring pre-existing CTL precursors and IgG reactive to many kinds of vaccine candidates, followed by administration. (4)(5)(6)(7)(8) In addition, we recently reported the benefits of the combination of this type of peptide vaccination with a low dose of estramustine phosphate in hormone refractory prostate cancer patients.(9) This chemoimmunotherapy may break through the impasse in the clinical efficacy of cancer vaccines.TS-1 is an oral fluoropyrimidine derivative consisting of Tegafur (FT) and two modulators, 5-chloro-2,4-dihydroxypyrimidine (CDHP) and potassium oxonate (Oxo). FT is a prodrug of 5-fluorouracil (5-FU) and CDHP is a reversible competitive inhibitor of an enzyme involved in the degradation of 5-FU. Therefore, the FT-derivative 5-FU remains in tumor tissue a long time, resulting in an enhanced antitumor effect.(10,11) Indeed, TS-1 has been reported to be effective at prolonging the survival of patients with advanced gastric cancer.(12) Furthermore, TS-1 can be administered as an oral formulation that permits treatment on an outpatient basis, leading to improvement in the quality of life (QOL) of patients. In the present study, we investigated the safety and immunological responses of personalized peptide vaccination in combination with the oral administration of TS-1 in advanced gastric or colorectal carcinoma patients. Materials and MethodsPatients and eligibility criteria. The study protocol was approved by the Institutional Ethical Review Boards of Hokkaido University, Okayama University and Kurume University. Complete written informed consent was obtained from all patients at the time of enrolment. According to the protocol, patients were confirmed to be HLA-A24 or HLA-A2 positive and had a histologically confirmed lesion of gastric or colorectal carcinoma. In HLA-A2 + patients, their HLA-A2 genotypes were determined using sequence-specific oligonucleotide DNA typing after polymerase chain reaction. All patients had failed to improve by prior chemotherapy with TS-1. The other eligibility criteria included an age of 85 years or less, serum creatinine of less than 1.4 mg/dL, bilirubin of less than 1.5 mg / dL, a platelet count of 100 000 µL or more, hemoglobin of 8.0 g / dL or more, and total white blood cell count (W...

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Identification of Lck-derived peptides capable of inducing HLA-A2-restricted and tumor-specific CTLs in cancer patients with distant metastases

Cited by 35 publications

References 30 publications

Characterization of tumor antigen peptide-specific T cells isolated from the neoplastic tissue of patients with gastric adenocarcinoma

Characterization of tumor antigen peptide-specific T cells isolated from the neoplastic tissue of patients with gastric adenocarcinoma

Identification of Lck-derived peptides applicable to anti-cancer vaccine for patients with human leukocyte antigen-A3 supertype alleles

Immunological evaluation of personalized peptide vaccination in combination with a 5‐fluorouracil derivative (TS‐1) for advanced gastric or colorectal carcinoma patients

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