Identification of HLA-A24 epitope peptides of carcinoembryonic antigen which induce tumor-reactive cytotoxic T lymphocyte

Nukaya, Ikuei; Yasumoto, Masazumi; Iwasaki, Tomoko; Ideno, Mitsuko; Sette, Alessandro; Celis, Esteban; Takesako, Kazutoh; Kato, Ikunoshin

doi:10.1002/(sici)1097-0215(19990105)80:1<92::aid-ijc18>3.0.co;2-m

Cited by 83 publications

(47 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the antigenic peptides restricted to HLA-A24 allele, most of which (90%) is HLA-A*2402 subtype and frequency (60%) expressed in Asians including Japanese (Nukaya et al, 1999). Thus, we have tried to identify a new p53 epitope peptide presented by HLA-A24.…”

Section: Discussionmentioning

confidence: 99%

“…The spontaneous release was determined by incubating the target cells alone in the absence of effectors, and the maximum release was obtained by incubating the targets with 1 N HCl. All determinants were done in triplicate, and the standard deviation error was consistently below 10% of the mean value (Nukaya et al, 1999).…”

Section: Ctl Assaymentioning

confidence: 99%

“…DCs were generated in vitro as described previously (Romani et al, 1994) (Romani and Gruner, 1994;Nukaya et al, 1999). Briefly, PBMCs isolated from a normal volunteer (HLA-A24) by FicollPaque (Pharmacia, Piscataway, NJ) were separated by adherence to a plastic tissue culture flask to enrich the monocyte fraction.…”

Section: Primary Ctl Induction Culturesmentioning

confidence: 99%

“…To obtain sufficient cell numbers for detailed characterization, CTL lines were expanded in tissue cultures following methods similar to the ones described by Walter et al (Walter, 1995;Salgauer et al, 1996;Nukaya et al, 1999). A total of 5 × 10 4 CTL were resuspended in 25 ml of RPMI/5% HS with 25 × 10 6 irradiated (3300 rads) PBMC and 5 × 10 6 irradiated (8000 rads) Epstein-Barr virus-transformed β-lymphoblastoid cell line EHM cells (HLA-A3/3) in the presence of 30 ng ml -1 of anti-CD3 MAb.…”

Section: Procedures Of Ctl Expansionmentioning

confidence: 99%

See 3 more Smart Citations

Generation of cytotoxic T cell responses to an HLA-A24 restricted epitope peptide derived from wild-type p53

et al. 2001

View full text Add to dashboard Cite

Mutations in the p53 gene are the most common genetic alterations found in human tumours, and these mutations result in high levels of p53 protein in the tumour cells. Since the expression levels of wild-type p53 in nonmalignant tissue are usually much lower in contrast, the p53 protein is an attractive target for cancer immunotherapy. We tested p53 encoded HLA-A24 binding peptides for their capacity to elicit anti-tumour cytotoxic T lymphocytes (CTL) in vitro. These peptides were in murine p53-derived cytotoxic peptides, which were being presented to CTL by H-2K d and H-2K b molecules, because the HLA-A24 peptide binding motifs were similar to the H-2K d and H-2K b . For CTL induction, we used CD8 + T lymphocytes from the peripheral blood mononuclear cells (PBMC) of healthy donors and the peptides from pulsed dendritic cells as antigen-presenting cells. We identified the peptide, p53-161 (AIYKQSQHM), which was capable of eliciting CTL lines that lysed tumour cells expressing HLA-A24 and p53. The effectors lysed C1RA24 cells (p53 + , HLA-A*2402 transfectant), but not their parental cell lines C1R (p53 + , HLA-A,B null cell). These results strongly indicate that the CTL exerts cytotoxic activity in HLA-A24's restricted manner. The identification of this novel p53 epitope for CTL offers the possibility to design and develop specific immunotherapeutic approaches for treating tumours with p53 mutation in HLA-A24-positive patients. © 2001 Cancer Research Campaign http://www.bjcancer.com

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Ctl Assaymentioning

confidence: 99%

Section: Primary Ctl Induction Culturesmentioning

confidence: 99%

Section: Procedures Of Ctl Expansionmentioning

confidence: 99%

See 2 more Smart Citations

Generation of cytotoxic T cell responses to an HLA-A24 restricted epitope peptide derived from wild-type p53

et al. 2001

View full text Add to dashboard Cite

show abstract

“…DCs were generated in vitro as described (Tsai et al, 1997;Nukaya et al, 1999). Briefly, PBMC isolated from a normal volunteer (HLA-A24 / A2) by Ficoll-Paque (Pharmacia, Piscataway, NJ) were separated by adherence to a plastic tissue culture flask so as to enrich them for the monocyte fraction.…”

Section: Primary Ctl Induction Culturesmentioning

confidence: 99%

Mapping the HLA-A24-restricted T-cell epitope peptide from a tumour-associated antigen HER2 / neu: possible immunotherapy for colorectal carcinomas

et al. 2001

View full text Add to dashboard Cite

Summary HER2 / neu is a potential antigen candidate for immunotherapy because of its correlation to a poor prognosis and high expressions in many kinds of epithelial tumours. Especially in the colorectal carcinomas, the higher expression of HER2 / neu is recognized in metastatic regions as well as in primary sites. Several CTL epitopes restricted by HLA-A2.1 and -A3 were identified so far, however epitopes restricted by HLA-A24, that is one of the most common allele in Japanese and Caucasians, have not been identified. In this paper, we showed identification of a CTL epitope peptide of HER2 / neu restricted by HLA-A24. HLA-A24 binding peptides selected by an analysis based on HLA-A24 binding motifs were determined for their binding affinities to HLA-A24 molecules. The peptide with a sequence of RWGLLLALL (position 8-16) named HE1 showed the highest affinity. We induced CTLs from CD8 + cells of HLA-A24 healthy donors by stimulation with HE1-pulsed autologous dendritic cells. The CTLs showed cytotoxic activity against not only the peptide-pulsed target cells but also HLA-A24 colorectal tumour cell lines that endogenously overexpressed HER2 / neu. The antigen-specificity was confirmed by cold target inhibition assay using HE1-pulsed target cells. In summary, HER2 / neu peptide, RWGLLLALL, may contribute to the induction of antitumour immunity with the peptide-based immunotherapy for the colorectal carcinomas.

show abstract

Identification of human antitumor cytotoxic T lymphocytes epitopes of recoverin, a cancer-associated retinopathy antigen, possibly related with a better prognosis in a paraneoplastic syndrome

et al. 2001

View full text Add to dashboard Cite

Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome, and the recoverinspecific autoantibody is suggested to contribute to the pathogenesis of retinopathy, including apoptosis of retinal cells. Because it is known that CAR + cancer patients have a preferable prognosis, we hypothesized that aberrantly expressed recoverin in cancer cells can become a target of cytotoxic T lymphocytes (CTL). Here we tested nine recoverin-derived HLA-A24-binding peptides for their capacity to elicit antitumor CTL. We observed recoverinspecific CTL responses in two HLA-A24 + CAR + cancer patients. In addition, the CTL responses were obtained from three of ten CARcancer patients and two of six healthy individuals. The CTL precursor frequency of CAR + cancer patients and that of CARcancer patients was higher than that of healthy individuals. Of nine recoverin peptides, R49 (QFQSIYAKF), R49.2 (QFQSIYAKFF), and R64 (AYAQHVFRSF) were discovered to induce the peptide-specific CTL. Taken together, our present data suggest that peripheral activation of recoverin-specific antitumor CTL is likely to contribute to the preferable prognosis of CAR + cancer patients. Moreover, in cases other than CAR + cancer patients, recoverin may offer the opportunity to design epitope-based immunotherapeutic approaches for treating HLA-A24 + cancer patients with a recoverin-expressing tumor.

show abstract

Identification of HLA-A24 epitope peptides of carcinoembryonic antigen which induce tumor-reactive cytotoxic T lymphocyte

Cited by 83 publications

References 28 publications

Generation of cytotoxic T cell responses to an HLA-A24 restricted epitope peptide derived from wild-type p53

Generation of cytotoxic T cell responses to an HLA-A24 restricted epitope peptide derived from wild-type p53

Mapping the HLA-A24-restricted T-cell epitope peptide from a tumour-associated antigen HER2 / neu: possible immunotherapy for colorectal carcinomas

Identification of human antitumor cytotoxic T lymphocytes epitopes of recoverin, a cancer-associated retinopathy antigen, possibly related with a better prognosis in a paraneoplastic syndrome

Contact Info

Product

Resources

About