GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Association for Cancer Research (AACR)  (24)
  • 1
    Online Resource
    Online Resource
    Up-regulation of GPR48 Induced by Down-regulation of p27 Kip1 Enhances Carcinoma Cell Invasiveness and Metastasis
    American Association for Cancer Research (AACR) ; 2006
    In:  Cancer Research Vol. 66, No. 24 ( 2006-12-15), p. 11623-11631
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 66, No. 24 ( 2006-12-15), p. 11623-11631
    Abstract: A reduced expression level of the cyclin-dependent kinase inhibitor p27Kip1 is associated with increased tumor malignancy and poor prognosis in individuals with various types of cancer. To investigate the basis for this relation, we applied microarray analysis to screen for genes differentially expressed between p27+/− and parental (p27+/+) HCT116 human colon carcinoma cells. Expression of the gene for G protein–coupled receptor 48 (GPR48) was increased in the p27+/− cells. Forced expression of GPR48 increased both in vitro invasive activity and lung metastasis potency of HCT116 cells. In contrast, depletion of endogenous GPR48 by RNA interference reduced the invasive potential of HeLa and Lewis lung carcinoma cells not only in vitro but also in vivo. Moreover, GPR48 expression was significantly associated with lymph node metastasis and inversely correlated with p27 expression in human colon carcinomas. GPR48 may thus play an important role in invasiveness and metastasis of carcinoma and might therefore represent a potential prognostic marker or therapeutic target. (Cancer Res 2006; 66(24): 11623-31)
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-06-2629
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2006
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Phase II Clinical Trial of Multiple Peptide Vaccination for Advanced Head and Neck Cancer Patients Revealed Induction of Immune Responses and Improved OS
    American Association for Cancer Research (AACR) ; 2015
    In:  Clinical Cancer Research Vol. 21, No. 2 ( 2015-01-15), p. 312-321
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 21, No. 2 ( 2015-01-15), p. 312-321
    Abstract: Purpose: The peptides derived from ideal cancer–testis antigens, including LY6K, CDCA1, and IMP3 (identified using genome-wide cDNA microarray analyses), were used in immunotherapy for head and neck squamous cell cancer (HNSCC). In this trial, we analyzed the immune response to and safety and efficacy of vaccine therapy. Experimental Design: A total of 37 patients with advanced HNSCC were enrolled in this trial of peptide vaccine therapy, and the OS, PFS, and immunologic response were evaluated using enzyme-linked ImmunoSpot (ELISPOT) and pentamer assays. The peptides were subcutaneously administered weekly with IFA. The primary endpoints were evaluated on the basis of differences between HLA-A*2402-positive [A24(+)] patients treated with peptide vaccine therapy and –negative [A24(−)] patients treated without peptide vaccine therapy among those with advanced HNSCC. Results: Our cancer vaccine therapy was well tolerated. The OS of the A24(+) vaccinated group (n = 37) was statistically significantly longer than that of the A24(−) group (n = 18) and median survival time (MST) was 4.9 versus 3.5 months, respectively; P & lt; 0.05. One of the patients exhibited a complete response. In the A24(+) vaccinated group, the ELISPOT assay identified LY6K-, CDCA1-, and IMP3-specific CTL responses in 85.7%, 64.3%, and 42.9% of the patients, respectively. The patients showing LY6K- and CDCA1-specific CTL responses demonstrated a longer OS than those without CTL induction. Moreover, the patients exhibiting CTL induction for multiple peptides demonstrated better clinical responses. Conclusions: The immune response induced by this vaccine may improve the prognosis of patients with advanced HNSCC. Clin Cancer Res; 21(2); 312–21. ©2014 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-14-0202
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    The Coordinated Actions of TIM-3 on Cancer and Myeloid Cells in the Regulation of Tumorigenicity and Clinical Prognosis in Clear Cell Renal Cell Carcinomas
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Immunology Research Vol. 3, No. 9 ( 2015-09-01), p. 999-1007
    Details
    In: Cancer Immunology Research, American Association for Cancer Research (AACR), Vol. 3, No. 9 ( 2015-09-01), p. 999-1007
    Abstract: Clear cell renal cell carcinoma (ccRCC) is one of most common cancers in urogenital organs. Although recent experimental and clinical studies have shown the immunogenic properties of ccRCC as illustrated by the clinical sensitivities to various immunotherapies, the detailed immunoregulatory machineries governing the tumorigenicity of human ccRCC remain largely obscure. In this study, we demonstrated the clinical significance and functional relevance of T-cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) expressed on tumor cells and myeloid cells in patients with ccRCC. TIM-3 expression was detected on cancer cells and CD204+ tumor-associated macrophages (TAM), and higher expression level of TIM-3 was positively correlated with shorter progression-free survival (PFS) in patients with ccRCC. We found that TIM-3 expression was detected on a large number of tumors, and there was significant correlation between an increased number of TAMs and high expression level of TIM-3 in patients with ccRCC. Furthermore, TIM-3 rendered RCC cells with the ability to induce resistance to sunitinib and mTOR inhibitors, the standard regimen for patients with ccRCC, as well as stem cell activities. TIM-3 expression was induced on CD14+ monocytes upon long-term stimulation with RCC cells, and TIM-3–expressing myeloid cells play a critical role in augmenting tumorigenic activities of TIM-3-negative RCC cells. More importantly, treatment with anti–TIM-3 mAb suppressed its tumorigenic effects in in vitro and in vivo settings. These findings indicate the coordinated action of TIM-3 in cancer cells and in myeloid cells regulates the tumorigenicity of human RCC. Cancer Immunol Res; 3(9); 999–1007. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 2326-6066 , 2326-6074
    URL: Article
    DOI: 10.1158/2326-6066.CIR-14-0156
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2732517-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Abstract 495: Immune response to XAGE-1b (GAGED2a) in NSCLC patients and its clinical relevance.
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 495-495
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 495-495
    Abstract: BACKGROUND:XAGE-1bis a cancer/testis (CT) antigen expressed highly in non-small cell lung cancer (NSCLC) with restricted expressiononly in testis in normal tissues. In this study, we investigated correlation of intensity of humoral and cellular immune responses against XAGE-1b and itsclinical relevance in NSCLC patients. MATERIALS AND METHODS:Peripheral bloodwas obtained from NSCLC patients who visited Kawasaki Medical School Hospital between 2005 and 2012 under written informed consent. Antibody response to XAGE-1bwas analyzed by ELISA using synthesized XAGE-1b protein. CD4 and CD8 T-cell responses were examined by IFN-γ ELISA and/or IFN-γcapture assay by FACS using 12-mer or 16-merXAGE-1b-overlapping peptides (OLPs) spanning the entire XAGE-1b (GAGED2a) protein. RESULTS: Antibody positive frequencies of total 362 NSCLC, 220 lung adenocarcinoma and 85 lung squamous cell carcinoma patients were 8.8% (32/362), 12.7% (28/220) and 1.2% (1/85), respectively. With antibody positive NSCLC patients, the patients showing high, intermediate and low antibody response was 7, 20 and 5, respectively. The frequency of XAGE-1b-reactive CD4 T-cells in patients showing high, intermediate and low antibody response was 5.5 ±2.1 x 10−5, 1.5 ±0.7 x 10−5 and & lt; 1.1 x 10−5, respectively. The frequency of XAGE-1b-reactive CD8 T-cells was 6.9 ±1.6 x 10−6, 4.6 ±1.6 x 10−6 and & lt; 1.1 x 10−6, respectively. The frequency of cytotoxic CD8 T-cells in IFN-γ secreting CD8 T-cells in response to XAGE-1b-peptide-pulsed autologous EBV-B cells in patients showing high and intermediate antibody responses was 59.0% and 4.8%, respectively.We evaluated overall survival (OS) time with 120 stage IIIB/IV lung adenocarcinoma patients. Median OS were 32.3 and 14.4 months in antibody-positive and negative patients(P-.039). There was no significant differencewith 1-year survival rate in antibody-positive (68.7%) and negative (55.6%)patients, but was significant with 3-year survival rate in 34.8% and 14.1% respectively. Furthermore, univariate and multivariable analyses showed XAGE-1b antibody response was independent prognostic factor. CONCLUSION:Our findings indicate that CT antigen XAGE-1b is highly immunogenic in NSCLC patients inducing antibody, and CD4 and CD8 T-cell responses and the immune response against XAGE-1b is beneficial for prognosis. Citation Format: Yoshihiro Ohue, Koji Kurose, Shingo Eikawa, Yu Mizote, Hirofumi Matsumoto, Midori Isobe, Akiko Uenaka, Minoru Fukuda, Eiichi Nakayama, Mikio Oka. Immune response to XAGE-1b (GAGED2a) in NSCLC patients and its clinical relevance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 495. doi:10.1158/1538-7445.AM2013-495
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2013-495
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Abstract 2689: XAGE-1b(GAGED2a) immunity in non-small cell lung cancer
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2689-2689
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2689-2689
    Abstract: BACKGROUND: Several cancer/testis(CT) antigens such as NY-ESO-1 antigen, etc., have been shown to elicit immune responses in cancer patients spontaneously. Because of their restricted expression in normal tissues and high immunogenicity, CT antigens have been thought to be attractive targets for cancer vaccine. We previously described XAGE-1b (GAGED2a), one of the CT-associated antigens, was predominantly expressed in lung adenocarcinoma by immunohistochemistry using XAGE-1b mAb (clone USO 9-13) and could elicit both humoral and cellular immune response in patients with non-small cell lung cancer (NSCLC). In this study, we established CD4 and CD8 T cell clones from PBMC in XAGE-1b antibody-positive patients and analyzed the antigen recognition. MATERIALS AND METHODS: Sera and PBMCs were obtained from NSCLC patients who visited Kawasaki Medical School Hospital between 2005 and 2010. Antibody response to XAGE-1b was analyzed by ELISA using synthesized XAGE-1b protein. CD4 and CD8 T cell responses against XAGE-1b were examined by IFN-γ ELISA and/or capture assay using 17 16- or 17-mer XAGE-1b-overlapping peptides (OLPs) spanning the entire XAGE-1b protein by FACS in antibody-positive patients. Cytotoxicity was analyzed by bioluminescence assay (GAPDH). RESULTS: Spontaneous CD4 and CD8 T cell responses were also detected in most of the antibody positive patients. Occurrence of antibody response, and CD4 and CD8 T cell responses in XAGE-1b (GAGED2a) antibody positive patients indicated strong immunogenicity of XAGE-1b (GAGED2a) antigen in NSCLC patients. Furthermore, We identified the minimal epitope peptide bound to HLA-DR4.1 and DP5 recognized by CD4 and those bound to HLA-A2, B61 and Cw1 recognized by CD8 T cell clones. CD4 and CD8 T cell clones recognized naturally processed XAGE-1b (GAGED2a) antigen on APC (antigen-presenting cell) and the CD8 T cell clone was stained with the peptide/MHCI tetramer and showed cytotoxicity against XAGE-1b (GAGED2a)-expressing, appropriate HLA class I expressing tumor cell line. CONCLUSION: Our findings indicate validity of XAGE-1b (GAGED2a) for cancer vaccine. Now we plan to global clinical trial of cancer vaccine against XAGE-1b in NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2689. doi:10.1158/1538-7445.AM2011-2689
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-2689
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Abstract B173: Preclinical characterization and antitumor efficacy of DS-5010, a highly potent and selective RET inhibitor
    American Association for Cancer Research (AACR) ; 2018
    In:  Molecular Cancer Therapeutics Vol. 17, No. 1_Supplement ( 2018-01-01), p. B173-B173
    Details
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 17, No. 1_Supplement ( 2018-01-01), p. B173-B173
    Abstract: Background: RET gene rearrangement has been detected in several cancers including 1-2% and 50% of non-small cell lung cancer (NSCLC) and papillary thyroid carcinoma, respectively, and it is known as a driver mutation. Several US Food and Drug Administration (FDA)-approved multi-tyrosine kinase inhibitors (MTKIs) have shown inhibitory effects on RET kinase activity and have been tested in several clinical studies. However, MTKIs do not appear potent enough to show clinical benefits. The FDA-approved MTKIs have been reported to exhibit dose-limiting toxicity (DLT) at doses below those suppressing RET kinase activity. Kinase insert domain receptor (KDR) inhibition especially leads to anti-angiogenesis-related DLT such as hypertension. Thus, the development of highly potent and selective second-generation RET inhibitors is desired. DS-5010 is an orally available small-molecule RET inhibitor that shows a specific and highly potent activity against RET and gatekeeper-mutated RET (RET-GKm) and slight KDR activity. In this study, we characterized the in vitro and in vivo activities of DS-5010. Results: In biochemical assays of 106 kinases, RET and platelet-derived growth factor receptor (PDGFR) alpha/beta were inhibited more than 80% by 193 nM DS-5010. The half-maximal inhibitory concentration (IC50) values of DS-5010 against RET, RET-GKm (V804L) were single digit nano-molar even under a condition of high concentration of ATP; besides it against KDR was more than 1000 nM. In a Ba/F3-RET subcutaneous tumor model, DS-5010 dosing at 10 mg/kg twice daily (bid) induced tumor regression. Moreover, DS-5010 exhibited a similar antitumor effect in a Ba/F3-RET-GKm (V804L) subcutaneous tumor model. In contrast, the FDA-approved MTKIs (cabozantinib, vandetanib, and alectinib) showed no significant antitumor effect on a Ba/F3-RET-GKm (V804L) subcutaneous tumor model. In an LC2/ad NSCLC xenograft model, which has the RET-CCDC6 fusion gene, DS-5010 dosing at 1 mg/kg thrice daily (tid) induced tumor regression. To predict acquired mutations against FDA-approved MTKIs, resistant clones were established by prolonged incubation of Ba/F3-RET cells with cabozantinib. A sequence analysis revealed that all the resistant clones possessed V804E mutation in the RET kinase domain and DS-5010 inhibited cell proliferation of Ba/F3-RET (V804E) mutation in the low nano-molar range. However, the FDA-approved MTKIs failed to show strong growth inhibitory effects (half-maximal growth inhibition [GI50]: 1584-5381 nM). Conclusion: These results indicate that DS-5010 has potent in vitro and in vivo activities against RET and RET-GKm, suggesting the potential usefulness of the compound for targeted therapy of cancers with RET gene rearrangements and mutations. Moreover, its potential effectiveness against acquired MTKI-resistant cells was also demonstrated. We are currently performing investigational new drug-enabling studies of DS-5010. Citation Format: Yasuyuki Kaneta, Takahiro Komatsu, Masashi Miyamoto, Megumi Goto, Hidenori Namiki, Yoshihiro Shibata, Hideaki Kageji, Hiroaki Inagaki, Kiyoshi Nakayama, Yuichi Tominaga, Takeshi Isoyama. Preclinical characterization and antitumor efficacy of DS-5010, a highly potent and selective RET inhibitor [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B173.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    URL: Article
    DOI: 10.1158/1535-7163.TARG-17-B173
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
    detail.hit.zdb_id: 2062135-8
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Abstract 518: Immunogenicity of cancer/testis antigen XAGE-1d in patients with non-small cell lung cancer (NSCLC)
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 518-518
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 518-518
    Abstract: BACKGROUND: Cancer/testis (CT) antigens expresses in various cancers and normal testis. Because of no expression of HLA class-I antigen in normal testis, CT antigens are promising molecular target for specific cancer immunotherapy. XAGE-1 gene has been identified as a CT-like antigen, and XAGE-1 gene has four alternative splice variants: XAGE-1a, XAGE-1b, XAGE-1c, and XAGE-1d. We previously reported that the transcript of XAGE-1a and XAGE-1b coded the same protein (GAGED2, isoform a, 81 amino acids) and the transcript of XAGE-1d coded another protein (GAGED2, isoform b, 69 amino acids). The first half of XAGE-1b and 1d protein (1-32 amino acids) is same sequence. On the other hand, XAGE-1c transcript codes some peptides but not a protein. Previously, immunogenic analyses of XAGE-1b have been performed because of its dominant expression, however, few analysis of XAGE-1d was performed. In this study, we investigated the immunogenicity of XAGE-1d in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Tumor tissue samples for extracting mRNA were obtained from NSCLC patients treated surgical resection at Nagasaki University Hospital during the period from 2005 to 2010. Sera and PBMCs were obtained from NSCLC patients who visited Kawasaki Medical School Hospital during the period from 2005 to 2010. Splising variants of XAGE-1 gene were analyzed by quantitative real-time PCR with specific TaqMan probe-primer sets. Antibody responses to XAGE-1d were analyzed by ELISA using synthesized XAGE-1b protein. In antibody-positive patients, CD4+ T-cell responses against XAGE-1d were examined by IFN-γ ELISA. Epitope-peptides recognized by XAGE-1d specific T-cells were determined by ELISA using XAGE-1d-overlapping peptides (OLPs). RESULTS: In quantitative real-time PCR, expression of XAGE-1d mRNA was observed in 16/38 specimens (42.1%) that were also positive with XAGE-1b mRNA. The correlation coefficiency of the expression was 0.8047. Protein expression of XAGE-1d was observed in cytoplasm, being different from that of XAGE-1b in the nucleus in lung cancer cell lines by immunohistochemical staining. Antibody against XAGE-1d was detected in lung cancer patients who were also positive with XAGE-1b antibody. By a limiting dilution, a CD4+ T-cell clone was obtained from PBMCs in a seropositive patient. HLA class II restricted recognition of XAGE-1d was confirmed using various allogeneic EBV-B cells as APC. 14-mer minimal epitope peptide was determined. CONCLUSION: The findings indicate that XAGE-1d co-expresses with XAGE-1b and is immunogenic in NSCLC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 518. doi:1538-7445.AM2012-518
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2012-518
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Phase Ia Study of FoxP3+ CD4 Treg Depletion by Infusion of a Humanized Anti-CCR4 Antibody, KW-0761, in Cancer Patients
    American Association for Cancer Research (AACR) ; 2015
    In:  Clinical Cancer Research Vol. 21, No. 19 ( 2015-10-01), p. 4327-4336
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 21, No. 19 ( 2015-10-01), p. 4327-4336
    Abstract: Purpose: FoxP3+ Tregs inhibit immune responses against tumors. KW-0761 is a humanized anti-human CCR4 monoclonal antibody (mAb) that has antibody-dependent cellular cytotoxicity activity. Depletion of CCR4-expressing FoxP3+ CD4 Tregs by KW-0761 infusion was investigated in solid cancer patients. Experimental Design: We conducted a phase Ia clinical trial of KW-0761 infusion in 7 lung and 3 esophageal cancer patients. Toxicity, clinical efficacy, changes in lymphocyte subpopulations, including Tregs, and induction of immune responses were analyzed. Results: The results showed that KW-0761 infusion in a dose range between 0.1 mg/kg and 1.0 mg/kg was safe and well tolerated. No dose-limiting toxicity was observed. Four of 10 patients showed stable disease during treatment and were long survivors. The monitoring of FoxP3+ Tregs in the peripheral blood mononuclear cells during treatment indicated efficient depletion of those cells, even at the lowest dose of 0.1 mg/kg used. The reduction in Th 1 CD4 T cells and CD8 T cells was limited, whereas a significant reduction was observed with Th 2 and Th 17 CD4 T cells. Immune responses to cancer/testis (CT) antigens and an autoantibody response to thyroid peroxidase were observed in some patients. Conclusions: The findings showed Tregs depletion and the possible occurrence of an immune response following KW-0761 infusion. Combined use of KW-0761 to deplete FoxP3+ Tregs with other immunotherapies, such as cancer vaccines or checkpoint inhibitors, is a promising approach to augment immune responses. Clin Cancer Res; 21(19); 4327–36. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-15-0357
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Abstract 1915: Enrichment of Tregs in migrated T-cells to IL-6- and IL-8-expressing tumors through induction of CXCR1 by IL-6
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 1915-1915
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 1915-1915
    Abstract: Background: Several mechanisms by which tumors evade the host immune response have been elucidated. A tumor modulates its antigenicity by immunoediting during development of an overt tumor, and frequently loses MHC and/or tumor antigen expression. Recently, it has been shown that regulatory T-cells were closely involved in immune impairment against tumors. Naturally occurring Foxp3+ CD25 high CD4 Tregs were observed in local tumor sites in some ovarian cancer patients and infiltration of those Tregs in the tumor correlated well with poor patient prognosis. Moreover, recently, an increase in the number of Tregs in the peripheral blood has been shown in advanced cancer patients and immune down-regulation systemically occurring in those patients is one cause of the ineffectiveness of immunization in clinical trials using cancer vaccines. The evidence suggests that it is necessary to regulate Tregs function and their accumulation to tumor local site for induction of effective immune response against tumors. Purpose: In this study, we investigated cytokine and chemokine production by tumor cell lines including 5 lung cancers, a malignant mesothelioma and a malignant melanoma recently established in our laboratory. We observed IL-8 production in all tumors and IL-6 production in one lung cancer, a malignant mesothelioma and a malignant melanoma. We investigated migration of Foxp3+ CD4 Tregs in PBMCs to those tumor cells using Transwell plates. Experimental Design: Cytokine and chemokine production was analyzed in tumor cell lines including 5 lung cancers, a malignant mesothelioma and a malignant melanoma recently established in our laboratory. IL-8 production was detected in all tumors and IL-6 production in 3 of them. We then investigated the role of IL-6 and IL-8 on migration of Foxp3+ CD4 Tregs to those tumor cells using Transwell plates. Induction of IL-8 receptor on Foxp3+ CD4 T-cells by IL-6 was investigated by flow cytometry and its role on their migration was examined by anti-IL-8R blocking. Results: We showed enrichment of Foxp3+ CD4 Tregs in migrated T-cells to both IL-6 and IL-8-producing tumors. Marked induction of CXCR1 (IL-8RA) expression was observed on Foxp3+ CD4 Tregs by the treatment with IL-6. Migration of IL-6-treated Foxp3+ CD4 T-cells to the tumors was blocked by the addition of anti-CXCR1. In fact, high level of IL-6 was detected in pleural effusion in most of lung cancer patients. Conclusions: Frequent production of IL-8 by the tumors and Treg migration to those tumors through induction of IL-8 receptor expression by IL-6 is one of the mechanisms for tumor escape. The findings indicate that the blocking of Treg migration by inhibiting IL-6-mediated IL-8 receptor expression could be a new strategy for tumor immunotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1915.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM10-1915
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Abstract 2394: Spontaneous immune responses against XAGE-1b in patients with non-small cell lung cancer (NSCLC)
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 2394-2394
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 2394-2394
    Abstract: BACKGROUND: Cancer/testis (CT) antigen is expressed only in the testis in normal adult tissues and in various types of cancers. There is no expression of MHC antigen in the testis. Therefore, CT antigen is thought to be a promising target for cancer immunotherapy. The XAGE-1 gene has been identified as a CT-like antigen and consists of several isoforms. We recently reported that XAGE-1b was predominantly expressed in lung adenocarcinoma by immunohistochemistry using XAGE-1b mAb (clone USO 9-13). In this study, we investigated humoral and cellular immune responses against XAGE-1b in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Sera and PBMCs were obtained from NSCLC patients who visited Kawasaki Medical School Hospital between 2005 and 2009. Antibody response to XAGE-1b was analyzed by ELISA using synthesized XAGE-1b protein. CD4 and CD8 T-cell responses against XAGE-1b were examined by IFN-γ ELISA and/or secretion assay using 17 16- or 17-mer XAGE-1b-overlapping peptides (OLPs) spanning the entire XAGE-1b protein in antibody-positive patients. Epitope peptides recognized by antibody and T-cells were determined by ELISA using XAGE-1b OLPs. RESULTS: Antibody positive frequencies of total 200 NSCLC patients and 69 stage IIIB/IV lung adenocarcinoma patients were 10.0% (20/200) and 18.8% (13/69), respectively. The peptide regions frequently recognized by the antibody were XAGE1b peptides 25-40, 29-44 and 33-48. CD4 and CD8 T-cell responses against XAGE-1b were observed in 14 (87.5%) of 16 patients and 6 (66.7%) of 9 patients, respectively, in the antibody-positive patients. No response was observed in 5 antibody-negative patients and 5 healthy donors. The XAGE-1b peptide regions dominantly recognized by CD4 and CD8 T-cells were XAGE-1b peptides 13-28 and 33-48 for CD4 and XAGE-1b peptide 29-44 for CD8. Furthermore, the minimal epitope peptides bound to HLA-DR4.1 and DP5 recognized by CD4 T-cell clones and those bound to HLA-A2 and Cw1 recognized by CD8 T-cell clones were determined. CONCLUSION: Our findings indicate that CT antigen XAGE-1b is highly immunogenic in NSCLC patients inducing antibody, and CD4 and CD8 T-cell responses. Thus, XAGE-1b is a promising target antigen for immunotherapy against lung adenocarcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2394.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM10-2394
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...