共查询到20条相似文献,搜索用时 31 毫秒
1.
Tatsuo Fujie Kouichirou Tahara Fumiaki Tanaka Masaki Mori Kazutou Takesako Tsuyoshi Akiyoshi 《International journal of cancer. Journal international du cancer》1999,80(2):169-172
Although several MAGE‐1 peptides have already been identified, the MAGE‐1‐encoded peptide presented by HLA‐A24, which is the most common allele in Japanese population and is also frequently present in Caucasians, might have a wide applicability for immunotherapy using these peptides. To identify this potential peptide, we examined the induction of specific cytotoxic T lymphocytes (CTL) from the peripheral‐blood mononuclear cells (PBMC) in HLA‐A24 healthy donors by in vitro stimulation with MAGE‐1‐encoded synthetic peptides with a binding affinity for HLA‐A24, by a simplified method. Of the 5 peptides tested, the highest HLA binder (NYKHCFPEI) was able to elicit CTL from unseparated PBMC by stimulation with freshly isolated, peptide‐pulsed PMBC as antigen‐presenting cells (APC) and by also using interleukin 7 and keyhole‐limpet hemocyanin for a primary culture. The induced CTL could thus lyse HLA‐A24 tumor cells expressing MAGE‐1, as well as the peptide‐pulsed target cells, in an HLA‐class‐I‐restricted manner. By using the MAGE‐1/HLA‐A24 peptide, NYKHCFPEI, we found it possible to immunize many more patients, especially Japanese patients, by means of such peptide‐based immunotherapeutic approaches to MAGE‐1‐positive malignant tumors. Int. J. Cancer 80:169–172, 1999. © 1999 Wiley‐Liss, Inc. 相似文献
2.
Objective
Vascular endothelial growth factor (VEGF) interaction with its receptor, VEGFR-3/Flt-4, regulates lymphangiogenesis. VEGFR-3/Flt-4 expression in cancer cells has been correlated with clinical stage, lymph node metastasis, and lymphatic invasion. The objective of this study is to identify a VEGFR-3/Flt-4-interacting peptide that could be used to inhibit VEGFR-3 for ovarian cancer therapy.Methods
The extracellular fragment of recombinant human VEGFR-3/Flt-4 (rhVEGFR-3/Flt-4) fused with coat protein pIII was screened against a phage-displayed random peptide library. Using affinity enrichment and enzyme-linked immunosorbent assay (ELISA) screening, positive clones of phages were amplified. Three phage clones were selected after four rounds of biopanning, and the specific binding of the peptides to rhVEGFR-3 was detected by ELISA and compared with that of VEGF-D. Immunohistochemistry and immunofluorescence analyses of ovarian cancer tissue sections was undertaken to demonstrate the specificity of the peptides.Results
After four rounds of biopanning, ELISA confirmed the specificity of the enriched bound phage clones for rhVEGFR-3. Sequencing and translation identified three different peptides. Non-competitive ELISA revealed that peptides I, II, and III had binding affinities for VEGFR-3 with Kaff (affinity constant) of 16.4±8.6 µg/mL (n=3), 9.2±2.1 µg/mL (n=3), and 174.8±31.1 µg/mL (n=3), respectively. In ovarian carcinoma tissue sections, peptide III (WHWLPNLRHYAS), which had the greatest binding affinity, also co-localized with VEGFR-3 in endothelial cells lining lymphatic vessels; its labeling of ovarian tumors in vivo was also confirmed.Conclusion
These finding showed that peptide III has high specificity and activity and, therefore, may represent a potential therapeutic approach to target VEGF-VEGFR-3 signaling for the treatment or diagnosis of ovarian cancer. 相似文献3.
Targeting acute myeloid leukemia with a proapoptotic peptide conjugated to a toll‐like receptor 2‐mediated cell‐penetrating peptide
下载免费PDF全文
![点击此处可从《International journal of cancer. Journal international du cancer》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Fang Hua Heng Lin Wei Sun Wen‐Bin Cao Xiao‐Ming Fu Jing Xie Jiao‐Jiao Yu Zhe Li Hong Liu Ming‐Zhe Han Zhuo‐Wei Hu 《International journal of cancer. Journal international du cancer》2014,134(3):692-702
Cell‐penetrating peptides provide a unique platform to create a new generation of cancer therapeutics with enhanced efficacy and diminished toxicity. In our study, enhanced expression of toll‐like receptor 2 (TLR2) was observed in acute myeloid leukemia (AML) cells. Screening of a phage display peptide library using Biopanning and Rapid Analysis of Selective Interactive Ligands (BRASIL) identified a TLR2‐binding peptide motif, Pep2. We show that the TLR2‐binding peptide motif targeted and penetrated into leukemia cells in a TLR2‐dependent manner. Moreover, a synthetic, chimeric peptide composed of the TLR2‐binding motif linked to a programmed cell death‐inducing sequence, D(KLAKLAK)2, induced apoptosis in AML cells with high TLR2 expression (TLR2high) but not in chronic myeloid leukemia (CML) cells with low TLR2 expression (TLR2low). The antileukemia activity of this chimeric peptide was confirmed in leukemia patient samples and an animal model of myeloid leukemia, as the development of leukemia was significantly delayed in mice with TLR2high AML compared to TLR2low CML NOD/SCID mice. TUNEL assays on bone marrow tissue slices revealed that the chimerical peptide induced leukemia cell apoptosis in a TLR2‐dependent manner. Together, our findings indicate that TLR2 is a potential therapeutic target for the prevention and treatment of AML, and the prototype, Pep2‐D(KLAKLAK)2, is a promising drug candidate in this setting. 相似文献
4.
Identification of CDCA1‐derived long peptides bearing both CD4+ and CD8+ T‐cell epitopes: CDCA1‐specific CD4+ T‐cell immunity in cancer patients
下载免费PDF全文
![点击此处可从《International journal of cancer. Journal international du cancer》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hirotake Tsukamoto Satoru Senju Sachiko Yoshimura Ryuji Osawa Yasuhiro Kuroda Masatoshi Hirayama Atsushi Irie Akinobu Hamada Hirofumi Jono Koji Yoshida Takuya Tsunoda Hirotsugu Kohrogi Yoshihiro Yoshitake Yusuke Nakamura Masanori Shinohara Yasuharu Nishimura 《International journal of cancer. Journal international du cancer》2014,134(2):352-366
We recently identified a novel cancer‐testis antigen, cell division cycle associated 1 (CDCA1) using genome‐wide cDNA microarray analysis, and CDCA1‐derived cytotoxic T lymphocyte (CTL)‐epitopes. In this study, we attempted to identify CDCA1‐derived long peptides (LPs) that induce both CD4+ helper T (Th) cells and CTLs. We combined information from a recently developed computer algorithm predicting HLA class II‐binding peptides with CDCA1‐derived CTL‐epitope sequences presented by HLA‐A2 (A*02:01) or HLA‐A24 (A*24:02) to select candidate CDCA1‐LPs encompassing both Th cell epitopes and CTL‐epitopes. We studied the immunogenicity of CDCA1‐LPs and the cross‐priming potential of LPs bearing CTL‐epitopes in both human in vitro and HLA‐class I transgenic mice in vivo. Then we analyzed the Th cell response to CDCA1 in head‐and‐neck cancer (HNC) patients before and after vaccination with a CDCA1‐derived CTL‐epitope peptide using IFN‐γ enzyme‐linked immunospot assays. We identified two CDCA1‐LPs, CDCA139–64‐LP and CDCA155–78‐LP, which encompass naturally processed epitopes recognized by Th cells and CTLs. CDCA1‐specific CTLs were induced through cross‐presentation of CDCA1‐LPs in vitro and in vivo. In addition, CDCA1‐specific Th cells enhanced induction of CDCA1‐specific CTLs. Furthermore, significant frequencies of CDCA1‐specific Th cell responses were detected after short‐term in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with CDCA1‐LPs in HNC patients (CDCA139–64‐LP, 74%; CDCA155–78‐LP, 68%), but not in healthy donors. These are the first results demonstrating the presence of CDCA1‐specific Th cell responses in HNC patients and underline the possible utility of CDCA1‐LPs for propagation of both CDCA1‐specific Th cells and CTLs. 相似文献
5.
Many clinical trials of peptide vaccines have been carried out since the first clinical trial of a melanoma antigen gene‐1‐derived peptide‐based vaccine was reported in 1995. The earlier generations of peptide vaccines were composed of one to several human leukocyte antigen class I‐restricted CTL‐epitope peptides of a single human leukocyte antigen type. Currently, various types of next‐generation peptide vaccines are under development. In this review, we focus on the clinical trials of the following categories of peptide vaccines mainly published from 2008 to 2012: (i) multivalent long peptide vaccines; (ii) multi‐peptide vaccines consisting of CTL‐ and helper‐epitopes; (iii) peptide cocktail vaccines; (iv) hybrid peptide vaccines; (v) personalized peptide vaccines; and (vi) peptide‐pulsed dendritic cell vaccines. (Cancer Sci 2013; 104: 15–21) 相似文献
6.
Xiangan Tu Jintao Zhuang Wenwei Wang Liang Zhao Liangyun Zhao Jiquan Zhao Chunhua Deng Shaopeng Qiu Yuanyuan Zhang 《Journal of experimental & clinical cancer research : CR》2011,30(1):105
Background
Specific peptide ligands to cell surface receptors have been extensively used in tumor research and clinical applications. Phage display technology is a powerful tool for the isolation of cell-specific peptide ligands. To screen and identify novel markers for renal cell carcinoma, we evaluated a peptide that had been identified by phage display technology.Methods
A renal carcinoma cell line A498 and a normal renal cell line HK-2 were used to carry out subtractive screening in vitro with a phage display peptide library. After three rounds of panning, there was an obvious enrichment for the phages specifically binding to the A498 cells, and the output/input ratio of phages increased about 100 fold. A group of peptides capable of binding specifically to the renal carcinoma cells were obtained, and the affinity of these peptides to the targeting cells and tissues was studied.Results
Through a cell-based ELISA, immunocytochemical staining, immunohistochemical staining, and immunofluorescence, the Phage ZT-2 and synthetic peptide ZT-2 were shown to specifically bind to the tumor cell surfaces of A498 and incision specimens, but not to normal renal tissue samples.Conclusion
A peptide ZT-2, which binds specifically to the renal carcinoma cell line A498 was selected from phage display peptide libraries. Therefore, it provides a potential tool for early diagnosis of renal carcinoma or targeted drug delivery in chemotherapy. 相似文献7.
Ryo Ueda Kozo Ohkusu‐Tsukada Noemi Fusaki Akio Soeda Takeshi Kawase Yutaka Kawakami Masahiro Toda 《International journal of cancer. Journal international du cancer》2010,126(4):919-929
Malignant gliomas are the most aggressive human primary brain tumors and are currently incurable. Immunotherapies have the potential to target glioma and glioma stem cells (GSCs) that are resistant to conventional therapies. We previously identified SOX6 as a human glioma antigen and demonstrated that vaccination with SOX6 DNA induced cytotoxic T lymphocytes (CTLs) specific for glioma, thereby exerting therapeutic antitumor responses in glioma‐bearing mice. In this study, we attempted to identify SOX6‐derived peptides as specific targets for effective and safe T‐cell‐mediated immunotherapy targeting SOX6‐positive glioma and GSCs. In vitro stimulation with human leukocyte antigen (HLA)‐A*2402 (A24)‐restricted peptides, RFENLGPQL (SOX6504) and PYYEEQARL (SOX6628) or the HLA‐A*0201 (A2)‐restricted peptide, ALFGDQDTV (SOX6447) was capable of inducing SOX6 peptide‐specific CTLs in peripheral blood mononuclear cells derived from healthy donors and glioma patients. These CTLs were able to lyse a majority of glioma cell lines and a GSC line derived from human glioblastoma in an HLA Class I‐restricted and an antigen‐dependent manner. Furthermore, peptide vaccines of SOX6628, which was conserved in the murine SOX6 protein and expected to bind to major histocompatibility complex (MHC) H‐2d, induced CTLs specific for SOX6628 in H‐2d mice. Normal autologous cells from mice, in which SOX6‐specific immune responses were generated, were not destroyed. These results suggest that these SOX6 peptides are potnetially immunogenic in HLA‐A24 or ‐A2 positive glioma patients and should be considered as a promising strategy for safe and effective T‐cell‐based immunotherapy of patients with gliomas. 相似文献
8.
In this study, a NCI-H1299 (Non-Small Cell Lung Cancer, NSCLC) and a normal lung cell line (Small Airway Epithelial Cells, SAEC) were used for the subtractive screening in vitro with a phage display-12 peptide library. After three rounds of panning, there was an obvious enrichment for the phages specifically binding to the NCI-H1299 cells, and the output/input ratio of phages increased about 875-fold (from 0.4 × 104 to 3.5 × 106). A group of peptides being capable of binding specifically to the NCI-H1299 cells were obtained, and the affinity of these peptides to bind to the targeted cells and tissues was studied. Through a cell-based ELISA, immunocytochemical staining, immunohistochemical staining, and immunofluorescence, a M13 phage isolated and identified from the above screenings, and a synthetic peptide ZS-1 (sequence EHMALTYPFRPP) corresponded to the sequence of the surface protein of the M13 phage were demonstrated to be capable of binding to the tumor cell surfaces of NCI-H1299 and A549 cell lines and biopsy specimens, but not to normal lungs tissue samples, other different cancer cells, or nontumor surrounding lung tissues. In conclusion, the peptide ZS-1 may be a potential candidate of biomarker ligands used for targeted drug delivery in therapy of lung cancer. 相似文献
9.
Kirstin Krensel Rosemarie B. Lichtner 《International journal of cancer. Journal international du cancer》1999,80(4):546-552
The effects of chronic EGF exposure on expression of the α2β1 collagen and α5β1 fibronectin receptor in a pair of human carcinoma cell lines (A431 and A549) with differential responses to EGF in a short‐term ECM‐cell adhesion assay were investigated. Treatment with EGF at 10 ng/ml for 24 hr increased on both cell lines the expression of the α2‐ but not the β1‐ or α5‐integrin sub‐units, and concomitantly cellular adhesion was increased on collagen IV but not on fibronectin. Increased collagen adhesion of A549 cells could be blocked by α2‐ and β1‐integrin‐sub‐unit antibodies down to control levels, while it was blocked by α2‐integrin‐sub‐unit antibody only by 60% and completely by the β1‐integrin‐sub‐unit antibody on A431 cells. EGF induced disparate shifts in cell morphologies (dome‐like structures, A431, vs. spindle‐like fibroblastoid, A549) with concomitant opposite changes in the expression/localization of E‐cadherin in cell‐cell contacts. This could be taken as an indication for cell‐type‐specific differential changes in the ratio of cell‐ECM vs. cell‐cell contacts. The EGF‐induced up‐regulation of the α2β1 integrin was instrumental in increasing collagen adhesion of A549 but only partly in the case of A431 cells, in which cells the α2β1 integrin may have additional functions besides serving as cell‐ECM receptor. Int. J. Cancer 80:546–552, 1999. © 1999 Wiley‐Liss, Inc. 相似文献
10.
Hitoshi Suzuki Hirofumi Hashimoto Makoto Kawasaki Miho Watanabe Hiroki Otsubo Toru Ishikura Hiroaki Fujihara Hideo Ohnishi Etsuro Onuma Hisafumi Yamada‐Okabe Yoh Takuwa Etsuro Ogata Toshitaka Nakamura Yoichi Ueta 《International journal of cancer. Journal international du cancer》2011,128(9):2215-2223
11.
Phase II clinical trial of peptide cocktail therapy for patients with advanced pancreatic cancer: VENUS‐PC study
下载免费PDF全文
![点击此处可从《Cancer science》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Nobuaki Suzuki Shoichi Hazama Haruo Iguchi Kazuhiro Uesugi Hiroaki Tanaka Kosei Hirakawa Atsushi Aruga Takashi Hatori Hidenobu Ishizaki Yuzo Umeda Toshiyoshi Fujiwara Tetsuya Ikemoto Mitsuo Shimada Kazuhiko Yoshimatsu Ryoichi Shimizu Hiroto Hayashi Koichiro Sakata Hiroko Takenouchi Hiroto Matsui Yoshitaro Shindo Michihisa Iida Yasunobu Koki Hideki Arima Hiroyuki Furukawa Tomio Ueno Shigefumi Yoshino Yusuke Nakamura Masaaki Oka Hiroaki Nagano 《Cancer science》2017,108(1):73-80
We previously conducted a phase I clinical trial combining the HLA‐A*2402‐restricted KIF20A‐derived peptide vaccine with gemcitabine for advanced pancreatic cancer (PC) and confirmed its safety and immunogenicity in cancer patients. In this study, we conducted a multicenter, single‐armed, phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide. We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine. Chemotherapy naïve PC patients were enrolled to evaluate primarily the 1‐year survival rate, and secondarily overall survival (OS), progression free survival (PFS), response rate (RR), disease control rate (DCR) and the peptide‐specific immune responses. All enrolled patients received therapy without the HLA‐A information, and the HLA genotypes were used for classification of the patients. Between June 2012 and May 2013, a total of 68 patients were enrolled. No severe systemic adverse effects of Grade 3 or higher related to these three peptides were observed. The 1‐year survival rates between the HLA‐A*2402‐matched and ‐unmatched groups were not significantly different. In the HLA‐A*2402 matched group, patients showing peptide‐specific CTL induction for KIF20A or VEGFR1 showed a better prognosis compared to those without such induction (P = 0.023, P = 0.009, respectively). In the HLA‐A*2402‐matched group, the patients who showed a strong injection site reaction had a better survival rate (P = 0.017) compared to those with a weak or no injection site reaction. This phase II study demonstrated that this therapeutic peptide cocktail might be effective in patients who demonstrate peptide‐specific immune reactions although predictive biomarkers are needed for patient selection in its further clinical application. 相似文献
12.
13.
Identification of novel Lck‐derived T helper epitope long peptides applicable for HLA‐A2+ cancer patients as cancer vaccine
下载免费PDF全文
![点击此处可从《Cancer science》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Satoko Matsueda Shigeki Shichijo Sayaka Nagata Chieko Seki Akira Yamada Masanori Noguchi Kyogo Itoh 《Cancer science》2015,106(11):1493-1498
The present study attempted to identify T helper epitope long peptides capable of inducing cytotoxic T lymphocytes (CTL) from Lck antigen (p56Lck), the src family tyrosine kinase, which is known to be aberrantly expressed in metastatic cancers cells, in order to develop a long peptide‐based cancer vaccine for HLA‐A2+ cancer patients. Based on the biding motif to the HLA‐DR and HLA‐A2 alleles, 94 peptides were prepared from the Lck antigen. These peptides were screened for their reactivity to immunoglobulin G (IgG) from plasma of cancer patients, followed by testing of their ability to induce both CD4+ and CD8+ T lymphocytes showing not only peptide‐specific IFN‐γ production but cytotoxicity against HLA‐A2+ cancer cells from peripheral blood mononuclear cells (PBMC) of HLA‐A2+ cancer patients. Among 94 peptides tested, the three T helper epitope long peptides and their inner CTL epitope short peptides with HLA‐A2 binding motifs were frequently recognized by IgG of cancer patients, and efficiently induced both CD4+ IFN‐γ+ and CD8+ IFN‐γ+ T lymphocytes. Patients' PBMC stimulated with these long peptides showed cytotoxicity against HLA‐A2+ Lck+ cancer cells in HLA‐class I and HLA‐class II dependent manners. These three peptides might be useful for long peptide‐based vaccines for HLA‐A2+cancer patients with Lck+ tumor cells. 相似文献
14.
Personalized peptide vaccination as second‐line treatment for metastatic upper tract urothelial carcinoma
下载免费PDF全文
![点击此处可从《Cancer science》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Shigetaka Suekane Kousuke Ueda Kiyoaki Nishihara Tetsuro Sasada Takuto Yamashita Noriko Koga Shigeru Yutani Shigeki Shichijo Kyogo Itoh Tsukasa Igawa Masanori Noguchi 《Cancer science》2017,108(12):2430-2437
This study investigated the applicability of personalized peptide vaccination (PPV) for patients with metastatic upper tract urothelial cancer (mUTUC) after failure of platinum‐based chemotherapy. In this single arm, open‐label, phase II clinical trial, patients with mUTUC received PPV at a single institution. Personalized peptide vaccination treatment used a maximum of four peptides chosen from 27 candidate peptides according to human leukocyte antigen types and peptide‐reactive IgG titers, for six s.c. injections weekly as one cycle. The safety of PPV, as well as its influence on host immunity and effect on overall survival were assessed. Forty‐eight patients were enrolled in this study. Personalized peptide vaccinations were well tolerated without severe adverse events. Median survival time was 7.3 months (95% confidence interval [CI], 5.3–13.1) with 13.0 months for patients receiving combined salvage chemotherapy (95% CI, 5.7–17.5) and 4.5 months for patients receiving PPV alone (95% CI, 1.7–10.1) (P = 0.080). Patients with positive CTL responses showed a significantly longer survival than patients with negative CTL responses (hazard ratio, 0.37; 95% CI, 0.16–0.85; P = 0.019). Multivariate Cox regression analysis showed that lower numbers of Bellmunt risk factors and lower levels of B‐cell activating factor were significantly associated with favorable overall survival for patients under PPV treatment. This study indicated that PPV for patients with mUTUC after failure of platinum‐based chemotherapy induced substantial peptide‐specific CTL responses without severe adverse events and has the potential to prolong survival when combined with salvage chemotherapy. UMIN Clinical Trials Registry ID: 000001854. 相似文献
15.
Immunological evaluation of peptide vaccination for cancer patients with the HLA‐A26 allele
下载免费PDF全文
![点击此处可从《Cancer science》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Shinjiro Sakamoto Satoko Matsueda Shinzo Takamori Uhi Toh Masanori Noguchi Shigeru Yutani Akira Yamada Shigeki Shichijo Teppei Yamada Shigetaka Suekane Kouichiro Kawano Tetsuro Sasada Noboru Hattori Nobuoki Kohno Kyogo Itoh 《Cancer science》2015,106(10):1257-1263
To develop a peptide vaccine for cancer patients with the HLA‐A26 allele, which is a minor population worldwide, we investigated the immunological responses of HLA‐A26+/A26+ cancer patients to four different CTL epitope peptides under personalized peptide vaccine regimens. In personalized peptide vaccine regimens, two to four peptides showing positive peptide‐specific IgG responses in pre‐vaccination plasma were selected from the four peptide candidates applicable for HLA‐A26+/A26+ cancer patients and administered s.c. Peptide‐specific CTL and IgG responses along with cytokine levels were measured before and after vaccination. Cell surface markers in PBMCs and plasma cytokine levels were also measured. In this study, 21 advanced cancer patients, including seven lung, three breast, two pancreas, and two colon cancer patients, were enrolled. Their HLA‐A26 genotypes were HLA‐A26:01 (n = 24), HLA‐A26:03 (n = 10), and HLA‐A26:02 (n = 8). One, 14, and 6 patients received two, three, and four peptides, respectively. Grade 1 or 2 skin reactions at the injection sites were observed in the majority of patients, but no severe adverse events related to the vaccination were observed. Peptide‐specific CTL responses were augmented in 39% or 22% of patients after one or two cycles of vaccination, respectively. Notably, peptide‐specific IgG were augmented in 63% or 100% of patients after one or two cycles of vaccination, respectively. Personalized peptide vaccines with these four CTL epitope peptides could be feasible for HLA‐A26+ advanced cancer patients because of their safety and higher rates of immunological responses. 相似文献
16.
Kanako Iseki Hiromi Matsunaga Nobukazu Komatsu Shigetaka Suekane Masanori Noguchi Kyogo Itoh Akira Yamada 《Cancer science》2010,101(10):2110-2114
Vaccine therapies are increasingly being used for the treatment of various diseases, and the antigen molecules themselves are being expanded from whole microorganisms to fine molecules such as peptides. Accordingly, there is a need for new adjuvants to support these new applications. In this paper, we used pharmaceutical grade mineral oil and sorbitan monooleate to develop a new oil adjuvant formula, NH2, and investigated its effects on peptide vaccination at both the pre‐clinical and clinical levels. The adjuvant effect of NH2 on peptide‐induced cellular immunity in mice was superior to that of Montanide ISA51VG, a commercially available incomplete Freund’s adjuvant for clinical use, although no significant difference was observed between the two adjuvants on peptide‐induced humoral immunity. The adjuvant effects of NH2 were also confirmed in a Phase‐I clinical trial of peptide vaccines for patients with advanced cancers. These results suggest that NH2 is a suitable adjuvant for peptide vaccination, particularly for cancer vaccines (Phase‐I clinical trial of pan‐HLA type personalized peptide vaccine for advanced cancer patients, UMIN clinical trial registry number: UMIN 000000619). (Cancer Sci 2010) 相似文献
17.
Immunological evaluation of peptide vaccination for cancer patients with the HLA ‐A11+ or ‐A33+ allele
下载免费PDF全文
![点击此处可从《Cancer science》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Shinjiro Sakamoto Satoko Matsueda Shinzo Takamori Uhi Toh Masanori Noguchi Shigeru Yutani Akira Yamada Shigeki Shichijo Teppei Yamada Shigetaka Suekane Kouichiro Kawano Masayasu Naitou Tetsuro Sasada Noboru Hattori Nobuoki Kohno Kyogo Itoh 《Cancer science》2017,108(4):598-603
The HLA‐A11 or ‐A33 allele is found in approximately 18% or 10% of the Asian population, respectively, but each of which is a minor allele worldwide, and therefore no clinical trials were previously conducted. To develop a therapeutic peptide vaccine for each of them, we investigated immunological responses of advanced cancer patients with the HLA‐A11+/A11+ (n = 18) or ‐A33+/A33+ (n = 13) allele to personalized peptide vaccine (PPV) regimens. The primary sites of HLA‐A11+/A11+ or ‐A33+/A33+ patients were the colon (n = 4 or 2), stomach (2 or 3), breast (3 or 2), lung and pancreas (2 or 2), and so on. For PPV, a maximum of four peptides were selected from nine different peptides capable of binding to HLA‐A11 and ‐A33 molecules based on the pre‐existing peptide‐specific IgG responses. There were no severe adverse events related to PPV. At the end of the first cycle, peptide‐specific CTL responses were augmented in 4/12 or 2/9 of HLA‐A11+/A11+ or ‐A33+/A33+ patients, while peptide‐specific IgG responses were augmented in 6/14 or 4/10 patients, respectively. Clinical responses consisted of four stable diseases and 14 progressive diseases in HLA‐A11+/A11+patients, versus seven and six in ‐A33+/A33+patients, respectively. Further clinical study of PPV could be recommended because of the safety and positive immunological responses. 相似文献
18.
Uhi Toh Sayaka Sakurai Shuko Saku Yuko Takao Mina Okabe Nobutaka Iwakuma Shigeki Shichijo Akira Yamada Kyogo Itoh Yoshito Akagi 《Cancer science》2020,111(8):2760-2769
We undertook an early phase II study of mixed 19‐peptide cancer vaccine monotherapy for 14 advanced metastatic triple‐negative breast cancer (mTNBC) patients refractory to systemic chemotherapy to develop a new type of cancer vaccine. The treatment protocol consisted of a weekly vaccination for 6 weeks, and there were no severe adverse events related to the vaccination throughout the trial. Increase of peptide‐specific IgG against the vaccinated human leukocyte antigen‐matched peptides, but not against the nonmatched peptides, was positively correlated with overall survival (OS) (P < .01). The median OS was 11.5 or 24.4 months in all 14 patients or the 10 patients who completed the vaccination. The patients with lower C‐reactive protein levels or 3 or fewer systemic chemotherapies were favorable candidates for this treatment. Advancement of this therapy to the next stage of study could be warranted based on the safety and immune boosting determined herein (clinical trial registration number: UMIN000014616). 相似文献
19.
Xiao N Cheng D Wang Y Chen L Liu X Dou S Liu G Liang M Hnatowich DJ Rusckowski M 《Cancer biology & therapy》2011,11(1):22-31
Purpose
Phage display was used to select novel peptides that specifically bind the TAG-72 antigen and with properties suitable for imaging TAG-72 positive cancers.Results
After three rounds of selection against TAG-72 and using two different elution conditions including a long elution, the consensus sequences FRE RCD KHP QKC TKF L and DPR HCQ KRV LPC PAW L were expressed on phages G3-15 and T3-15 respectively. ELISA, fluorescence-activated cell sorting analysis and fluorescence microscopy provided evidence that both phages specifically bound TAG-72 in vitro. Both peptides are stable in 37°C serum. By a cell binding competition assay, the IC50 for T3-15 was measured as 0.29 nM and therefore 36-fold higher affinity than G3-15 at 10.32 nM. The biodistribution in mice carrying LS-174T tumors in one thigh were similar for both 99mTc-peptides at 30 min, but at 90 min the 99mTc-T3-15 peptide accumulated almost three times higher in the tumor. The SPECT/CT images were consistent with the biodistribution results.Procedures
The f88-4/Cys6 phage library and two different elution conditions were used to identify two new higher affinity binding peptides for the TAG-72 antigen. One, was a single brief elution with pH 2.2 glycine buffer and the second began with the glycine elution but was followed with a longer elution with Tris buffered saline (TBS) at pH 7.4. The phages that bound TAG-72 were evaluated by fluorescence-activated cell sorting analysis using TAG-72 positive LS-174T cells and confirmed by immunofluorescence imaging. The consensus peptides displayed on the selected phages were synthesized and conjugated with NHS-MAG3 for radiolabeling with 99mTc. The IC50 for TAG-72 binding was evaluated by cell binding competition in vitro while binding affinity was evaluated in vivo by necropsy and SPECT/CT imaging in a tumor mouse model.Conclusion
We have identified a peptide with a sub nanomolar inhibition constant for the TAG-72 antigen that may have applications in cancer imaging.Key words: phage display, TAG-72 antigen, peptide, colon cancer tumor cell LS-174T 相似文献20.
Mari Kielosto Pirjo Nummela Kristiina Järvinen Miao Yin Erkki Hölttä 《International journal of cancer. Journal international du cancer》2009,125(5):1065-1073
Understanding the mechanisms of tumor cell invasion is essential for our attempts to prevent cancer deaths. We screened by DNAmicroarrays the c‐Jun‐ and transformation‐related gene expression changes in S‐adenosylmethionine decarboxylase (AdoMetDC)‐overexpressing mouse fibroblasts that are highly invasive in vivo, and their derivatives expressing a tetracycline‐inducible dominant‐negative mutant of c‐Jun (TAM67) or c‐Jun shRNA. Among the small set of target genes detected were integrins α6 and β7, cathepsin L and thymosin β4, all upregulated in the AdoMetDC‐transformed cells and downregulated upon reversal of transformation by TAM67 or c‐Jun shRNA. The upregulation of integrin α6 subunit, pairing with integrin β1, endowed the transformed cells with the capability to attach to basement membrane laminin and to spread. Further, inhibition of integrin α6 or β1 function with neutralizing antibodies blocked the invasiveness of AdoMetDC‐transformants and human HT‐1080 fibrosarcoma cells in three‐dimensional Matrigel. Moreover, immunohistochemical analyses showed strong integrin α6 staining in high‐grade human fibrosarcomas. Our data show that c‐Jun can regulate all three key steps of invasion: cell adhesion (integrin α6), basement membrane/extracellular matrix degradation (cathepsin L) and cell migration (thymosin β4). In addition, this is the first study to associate integrin β7, known as a leukocyte‐specific integrin binding to endothelial/epithelial cell adhesion molecules, with the transformed phenotype in cells of nonleukocyte origin. As tumor cell invasion is a prerequisite for metastasis, the observed critical role of integrin α6β1 in fibrosarcoma cell invasion/spreading allures testing antagonists to integrin α6β1, alone or combined with inhibitors of cathepsin L and thymosin β4, as chemotherapeutic agents. © 2009 UICC 相似文献