The Experts below are selected from a list of 54717 Experts worldwide ranked by ideXlab platform
Yusuke Nakamura - One of the best experts on this subject based on the ideXlab platform.
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Immunotherapy with Cancer Peptides in combination with intravesical bacillus Calmette–Guerin for patients with non-muscle invasive bladder Cancer
Cancer Immunology Immunotherapy, 2018Co-Authors: Wataru Obara, Yusuke Nakamura, Hiromitsu Mimata, Isao Hara, Yoichiro Kato, Renpei Kato, Keiji Inoue, Fuminori Sato, Tomoaki FujiokaAbstract:Purpose A phase I study using two Peptide vaccines derived from M phase phosphoprotein 1 (MPHOSPH1) and DEP domain containing 1 (DEPDC1) demonstrated promising results for the treatment of advanced bladder Cancer. Therefore, we further tested the ability of these Peptides to prevent recurrence after transurethral resection of the bladder tumor in patients with non-muscle invasive bladder Cancer (NMIBC). Materials and methods 127 patients were enrolled in a multicenter, non-randomized phase II clinical trial. The primary endpoint was recurrence-free survival (RFS) rate, and secondary endpoints were safety and immunological response. HLA-A24-restricted Peptides were subcutaneously administered in addition to intravesical BCG therapy. The exploratory endpoint evaluated differences of RFS rate between HLA-A*2402-positive (A24(+)) and -negative (A24(−)) groups. Results A 2-year RFS rate in all patients was 74.0%. The RFS rate in the A24(+) group ( n = 75) and in the A24(−) group ( n = 52) were 76.0 and 71.2%, respectively. This vaccine therapy was well-tolerated and feasible. MPHOSPH1 and DEPDC1 Peptide-specific cytotoxic T lymphocyte responses were observed in 75.8 and 77.5% of the A24(+) group, respectively. Patients having both Peptide-specific CTL responses showed significantly better RFS than patients without CTL response ( P = 0.014). In the A24(+) group, patients who had positive reaction at the injection sites (RAI) had significantly lower rates of recurrence than RAI-negative patients ( P = 0.0019). Conclusions Cancer Peptide vaccines in combination with intravesical BCG therapy demonstrated good immunogenicity and safety, and may provide benefit for preventing recurrence of NMIBC.
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immunotherapy with Cancer Peptides in combination with intravesical bacillus calmette guerin for patients with non muscle invasive bladder Cancer
Cancer Immunology Immunotherapy, 2018Co-Authors: Wataru Obara, Yusuke Nakamura, Hiromitsu Mimata, Isao Hara, Yoichiro Kato, Renpei Kato, Keiji Inoue, Fuminori Sato, Tomoaki FujiokaAbstract:Purpose A phase I study using two Peptide vaccines derived from M phase phosphoprotein 1 (MPHOSPH1) and DEP domain containing 1 (DEPDC1) demonstrated promising results for the treatment of advanced bladder Cancer. Therefore, we further tested the ability of these Peptides to prevent recurrence after transurethral resection of the bladder tumor in patients with non-muscle invasive bladder Cancer (NMIBC). Materials and methods 127 patients were enrolled in a multicenter, non-randomized phase II clinical trial. The primary endpoint was recurrence-free survival (RFS) rate, and secondary endpoints were safety and immunological response. HLA-A24-restricted Peptides were subcutaneously administered in addition to intravesical BCG therapy. The exploratory endpoint evaluated differences of RFS rate between HLA-A*2402-positive (A24(+)) and -negative (A24(-)) groups. Results A 2-year RFS rate in all patients was 74.0%. The RFS rate in the A24(+) group (n = 75) and in the A24(-) group (n = 52) were 76.0 and 71.2%, respectively. This vaccine therapy was well-tolerated and feasible. MPHOSPH1 and DEPDC1 Peptide-specific cytotoxic T lymphocyte responses were observed in 75.8 and 77.5% of the A24(+) group, respectively. Patients having both Peptide-specific CTL responses showed significantly better RFS than patients without CTL response (P = 0.014). In the A24(+) group, patients who had positive reaction at the injection sites (RAI) had significantly lower rates of recurrence than RAI-negative patients (P = 0.0019). Conclusions Cancer Peptide vaccines in combination with intravesical BCG therapy demonstrated good immunogenicity and safety, and may provide benefit for preventing recurrence of NMIBC.
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quantitative t cell repertoire analysis by deep cdna sequencing of t cell receptor α and β chains using next generation sequencing ngs
OncoImmunology, 2014Co-Authors: Hua Fang, Yataro Daigo, Rui Yamaguchi, Satoru Miyano, Chizu Tanikawa, Koichi Matsuda, Seiya Imoto, Yusuke NakamuraAbstract:Immune responses play a critical role in various disease conditions including Cancer and autoimmune diseases. However, to date, there has not been a rapid, sensitive, comprehensive, and quantitative analysis method to examine T-cell or B-cell immune responses. Here, we report a new approach to characterize T cell receptor (TCR) repertoire by sequencing millions of cDNA of TCR α and β chains in combination with a newly-developed algorithm. Using samples from lung Cancer patients treated with Cancer Peptide vaccines as a model, we demonstrate that detailed information of the V-(D)-J combination along with complementary determining region 3 (CDR3) sequences can be determined. We identified extensive abnormal splicing of TCR transcripts in lung Cancer samples, indicating the dysfunctional splicing machinery in T lymphocytes by prior chemotherapy. In addition, we found three potentially novel TCR exons that have not been described previously in the reference genome. This newly developed TCR NGS platform can be applied to better understand immune responses in many disease areas including immune disorders, allergies, and organ transplantations.
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Abstract 3568: Quantitative t cell receptor (tcr) repertoire analysis by next-generation sequencing (ngs) in non-small cell lung Cancer patients treated with therapeutic Cancer Peptide vaccines
Molecular and Cellular Biology, 2014Co-Authors: Hua Fang, Yataro Daigo, Rui Yamaguchi, Xiao Liu, Satoru Miyano, Yusuke NakamuraAbstract:Cancer immunotherapy is expected to become one of the major treatment options of Cancer, and there is lots of enthusiasm for the development of therapeutic Cancer vaccines. To better understand the molecular mechanism of action of therapeutic Cancer Peptide vaccines and also to better monitor patients9 immunological response as a predictive biomarker, a fast, sensitive, comprehensive, and quantitative method to characterize T lymphocytes is highly desired. However, TCR repertoire diversity and clonotype follow-up after Cancer vaccination represent a major challenge due to the enormous complexity of the TCR that characterizes individual T cell clones. Here, we demonstrated a new high throughput sequencing method to investigate the detailed genetic profiling of the TCR repertoire of millions of peripheral T lymphocytes from non-small cell lung Cancer (NSCLC) patients who had been treated with Cancer vaccine cocktail of Peptides derived from CDCA1, URLC10, and KIF20A. The new technology of cDNA sequences of TCR α and β chains using next generation DNA sequencer (Ion Torrent Personal Genome Machine (PGM) with 400bp sequencing chemistry) enabled us to assess the comprehensive TCR α and β repertoire information in an unbiased way. We also developed a novel algorithm ‘VDJ decomposition with soft-clipping’ that allowed us to identify the rearranged V-(D)-J regions in both TCR α and β chains, to analyze non-template nucleotides added at the junction sites, and also to determine the exact length and sequence of the complement determining region 3 (CDR3). In total, 16 samples from 5 NSCLC patients with different time points (before and after treatment) were analyzed for both TCR α and β repertoire. We obtained average 239,689 (range: 103,851 - 329,817) VJ identified reads for TCR α sequences and 499,210 (range: 193,753 - 982,040) VDJ identified reads for TCR β sequences. Significant increases of specific TCRβ CDR3 sequences were observed in patients showing stable condition after vaccine treatment. In patient #1 with long stable disease (SD) after treatment, two enriched clones of CASSSLQNIQYF and CASSPSVGLAGVAQKETQYF were present after vaccine treatment, suggesting those clones might represent Peptide-specific cytotoxic T lymphocytes. Similarly, enriched CDR3 clones of CASTVRQKDGYTF and CSVGAYRGETQYF were observed in patient #3 and #5 at SD condition. In conclusion, this newly-developed NGS technology with the novel algorism should contribute to the better understanding of the immune responses in patients treated with immunotherapy. Our approach can also be applied for the investigation of a wide range of immune-related disorders including rejection after organ transplantation. Citation Format: Hua Fang, Rui Yamaguchi, Xiao Liu, Yataro Daigo, Satoru Miyano, Yusuke Nakamura. Quantitative t cell receptor (tcr) repertoire analysis by next-generation sequencing (ngs) in non-small cell lung Cancer patients treated with therapeutic Cancer Peptide vaccines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3568. doi:10.1158/1538-7445.AM2014-3568
Wataru Obara - One of the best experts on this subject based on the ideXlab platform.
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Phase II open-label study of S-588410 as maintenance monotherapy after first-line platinum-containing chemotherapy in patients with advanced or metastatic urothelial carcinoma.
Journal of Clinical Oncology, 2021Co-Authors: Syed A. Hussain, Wataru Obara, Nobuaki Shimizu, Toshinari Yamasaki, Satoru Takashima, Takahiro Hasegawa, Motofumi Iguchi, Kenji Igarashi, Osamu Ogawa, Tomoaki FujiokaAbstract:440Background: S-588410 is a Cancer Peptide vaccine composed of 5 human leukocyte antigen (HLA)-A*24:02-restricted epitope Peptides derived from 5 Cancer-testis antigens: DEPDC1, MPHOSPH1, URLC10, ...
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Immunotherapy with Cancer Peptides in combination with intravesical bacillus Calmette–Guerin for patients with non-muscle invasive bladder Cancer
Cancer Immunology Immunotherapy, 2018Co-Authors: Wataru Obara, Yusuke Nakamura, Hiromitsu Mimata, Isao Hara, Yoichiro Kato, Renpei Kato, Keiji Inoue, Fuminori Sato, Tomoaki FujiokaAbstract:Purpose A phase I study using two Peptide vaccines derived from M phase phosphoprotein 1 (MPHOSPH1) and DEP domain containing 1 (DEPDC1) demonstrated promising results for the treatment of advanced bladder Cancer. Therefore, we further tested the ability of these Peptides to prevent recurrence after transurethral resection of the bladder tumor in patients with non-muscle invasive bladder Cancer (NMIBC). Materials and methods 127 patients were enrolled in a multicenter, non-randomized phase II clinical trial. The primary endpoint was recurrence-free survival (RFS) rate, and secondary endpoints were safety and immunological response. HLA-A24-restricted Peptides were subcutaneously administered in addition to intravesical BCG therapy. The exploratory endpoint evaluated differences of RFS rate between HLA-A*2402-positive (A24(+)) and -negative (A24(−)) groups. Results A 2-year RFS rate in all patients was 74.0%. The RFS rate in the A24(+) group ( n = 75) and in the A24(−) group ( n = 52) were 76.0 and 71.2%, respectively. This vaccine therapy was well-tolerated and feasible. MPHOSPH1 and DEPDC1 Peptide-specific cytotoxic T lymphocyte responses were observed in 75.8 and 77.5% of the A24(+) group, respectively. Patients having both Peptide-specific CTL responses showed significantly better RFS than patients without CTL response ( P = 0.014). In the A24(+) group, patients who had positive reaction at the injection sites (RAI) had significantly lower rates of recurrence than RAI-negative patients ( P = 0.0019). Conclusions Cancer Peptide vaccines in combination with intravesical BCG therapy demonstrated good immunogenicity and safety, and may provide benefit for preventing recurrence of NMIBC.
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immunotherapy with Cancer Peptides in combination with intravesical bacillus calmette guerin for patients with non muscle invasive bladder Cancer
Cancer Immunology Immunotherapy, 2018Co-Authors: Wataru Obara, Yusuke Nakamura, Hiromitsu Mimata, Isao Hara, Yoichiro Kato, Renpei Kato, Keiji Inoue, Fuminori Sato, Tomoaki FujiokaAbstract:Purpose A phase I study using two Peptide vaccines derived from M phase phosphoprotein 1 (MPHOSPH1) and DEP domain containing 1 (DEPDC1) demonstrated promising results for the treatment of advanced bladder Cancer. Therefore, we further tested the ability of these Peptides to prevent recurrence after transurethral resection of the bladder tumor in patients with non-muscle invasive bladder Cancer (NMIBC). Materials and methods 127 patients were enrolled in a multicenter, non-randomized phase II clinical trial. The primary endpoint was recurrence-free survival (RFS) rate, and secondary endpoints were safety and immunological response. HLA-A24-restricted Peptides were subcutaneously administered in addition to intravesical BCG therapy. The exploratory endpoint evaluated differences of RFS rate between HLA-A*2402-positive (A24(+)) and -negative (A24(-)) groups. Results A 2-year RFS rate in all patients was 74.0%. The RFS rate in the A24(+) group (n = 75) and in the A24(-) group (n = 52) were 76.0 and 71.2%, respectively. This vaccine therapy was well-tolerated and feasible. MPHOSPH1 and DEPDC1 Peptide-specific cytotoxic T lymphocyte responses were observed in 75.8 and 77.5% of the A24(+) group, respectively. Patients having both Peptide-specific CTL responses showed significantly better RFS than patients without CTL response (P = 0.014). In the A24(+) group, patients who had positive reaction at the injection sites (RAI) had significantly lower rates of recurrence than RAI-negative patients (P = 0.0019). Conclusions Cancer Peptide vaccines in combination with intravesical BCG therapy demonstrated good immunogenicity and safety, and may provide benefit for preventing recurrence of NMIBC.
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A phase I/II study of Cancer Peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder.
Annals of oncology : official journal of the European Society for Medical Oncology, 2017Co-Authors: Wataru Obara, Masatoshi Eto, Hiromitsu Mimata, Kenjiro Kohri, N. Mitsuhata, I. Miura, Taro Shuin, Tsuneharu Miki, Takuya Koie, H. FujimotoAbstract:ABSTRACT Background S-288310, a Cancer Peptide vaccine composed of two HLA-A*24:02-restricted Peptides derived from two oncoantigens, DEP domain-containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1), was investigated in urothelial carcinoma (UC) of the bladder. Patients and methods Thirty eight HLA-A*24:02-positive patients with progressive UC were enrolled in this study. In the phase I part of the study, three patients each were treated with S-288310 at 1 mg or 2 mg/Peptide subcutaneously once a week to evaluate safety and tolerability. In the phase II, 32 patients were randomized to receive either 1 mg or 2 mg to evaluate the difference in cytotoxic T lymphocytes (CTL) induction and safety. Results S-288310 was safe and well tolerated in the phase I. Of 27 patients evaluable for immune responses in the phase II, there was no difference in CTL induction rate between the 1 mg (100%) and 2 mg (80.0%) groups. Of 32 patients receiving S-288310 in the phase II, the most frequent drug-related AE was the injection site reaction that was observed in 29 patients (90.6%), but none of the patients discontinued administration due to these reactions and no dose relationship in the frequency and severity was observed. The objective response rate of the 32 patients was 6.3% and the disease control rate was 56.3%. The median overall survival (OS) rates for patients vaccinated with S-288310 after one regimen of chemotherapy, 2 regimens, or 3 or more were 14.4, 9.1 and 3.7 months, respectively, and 32.2% of patients post first-line treatment were alive at 2 years. OS of patients who showed CTL induction to both Peptides was longer than that of those with CTL induction to no or one Peptide. Conclusion S-288310 was well-tolerated and effectively induced Peptide-specific CTLs, which were correlated with longer survival for patients with UC of the bladder. Trial registration ID JapicCTI-090980
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Adjuvant Cancer Peptide vaccine treatment with intravesical BCG therapy for non-muscle-invasive bladder Cancer.
Journal of Clinical Oncology, 2013Co-Authors: Wataru ObaraAbstract:e15587 Background: We previously reported safety and high immunogenicity of Peptide vaccine treatment using two novel Peptides derived from oncoantigens, M phase phosphoprotein 1 (MPHOSPH1) and DEP...
Rob A. E. M. Tollenaar - One of the best experts on this subject based on the ideXlab platform.
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Improved classification of breast Cancer Peptide and protein profiles by combining two serum workup procedures
Journal of Cancer Research and Clinical Oncology, 2012Co-Authors: Berit Velstra, Yuri E. M. Burgt, Bart J. Mertens, Wilma E. Mesker, André M. Deelder, Rob A. E. M. TollenaarAbstract:Purpose Detection of breast Cancer at early stage increases patient’s survival. Mass spectrometry-based protein analysis of serum samples is a promising approach to obtain biomarker profiles for early detection. A combination of commonly applied solid-phase extraction procedures for clean-up may increase the number of detectable Peptides and proteins. In this study, we have evaluated whether the classification performance of breast Cancer profiles improves by using two serum workup procedures. Methods Serum samples from 105 breast Cancer patients and 202 healthy volunteers were processed according to a standardized protocol implemented on a high-end liquid-handling robot. Peptide and protein enrichments were carried out using weak-cation exchange (WCX) and reversed-phase (RP) C18 magnetic beads. Profiles were acquired on a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer. In this way, two different biomarker profiles were obtained for each serum sample, yielding a WCX- and RPC18-dataset. Results The profiles were statistically evaluated with double cross-validation. Classification results of WCX- and RPC18-datasets were determined for each set separately and for the combination of both sets. Sensitivity and specificity were 82 and 87 % (WCX) and 73 and 93 % (RPC18) for the individual workup procedures. These values increased up to 84 and 95 %, respectively, upon combining the data. Conclusion It was found that MALDI-TOF Peptide and protein profiles can be used for classification of breast Cancer with high sensitivity and specificity. The classification performance even improved when two workup procedures were applied, since these provide a greater number of features (proteins).
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Improved classification of breast Cancer Peptide and protein profiles by combining two serum workup procedures.
Journal of cancer research and clinical oncology, 2012Co-Authors: Berit Velstra, Wilma E. Mesker, André M. Deelder, Yuri E. M. Van Der Burgt, Bart Mertens, Rob A. E. M. TollenaarAbstract:Purpose Detection of breast Cancer at early stage increases patient’s survival. Mass spectrometry-based protein analysis of serum samples is a promising approach to obtain biomarker profiles for early detection. A combination of commonly applied solid-phase extraction procedures for clean-up may increase the number of detectable Peptides and proteins. In this study, we have evaluated whether the classification performance of breast Cancer profiles improves by using two serum workup procedures.
Hua Fang - One of the best experts on this subject based on the ideXlab platform.
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quantitative t cell repertoire analysis by deep cdna sequencing of t cell receptor α and β chains using next generation sequencing ngs
OncoImmunology, 2014Co-Authors: Hua Fang, Yataro Daigo, Rui Yamaguchi, Satoru Miyano, Chizu Tanikawa, Koichi Matsuda, Seiya Imoto, Yusuke NakamuraAbstract:Immune responses play a critical role in various disease conditions including Cancer and autoimmune diseases. However, to date, there has not been a rapid, sensitive, comprehensive, and quantitative analysis method to examine T-cell or B-cell immune responses. Here, we report a new approach to characterize T cell receptor (TCR) repertoire by sequencing millions of cDNA of TCR α and β chains in combination with a newly-developed algorithm. Using samples from lung Cancer patients treated with Cancer Peptide vaccines as a model, we demonstrate that detailed information of the V-(D)-J combination along with complementary determining region 3 (CDR3) sequences can be determined. We identified extensive abnormal splicing of TCR transcripts in lung Cancer samples, indicating the dysfunctional splicing machinery in T lymphocytes by prior chemotherapy. In addition, we found three potentially novel TCR exons that have not been described previously in the reference genome. This newly developed TCR NGS platform can be applied to better understand immune responses in many disease areas including immune disorders, allergies, and organ transplantations.
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Abstract 3568: Quantitative t cell receptor (tcr) repertoire analysis by next-generation sequencing (ngs) in non-small cell lung Cancer patients treated with therapeutic Cancer Peptide vaccines
Molecular and Cellular Biology, 2014Co-Authors: Hua Fang, Yataro Daigo, Rui Yamaguchi, Xiao Liu, Satoru Miyano, Yusuke NakamuraAbstract:Cancer immunotherapy is expected to become one of the major treatment options of Cancer, and there is lots of enthusiasm for the development of therapeutic Cancer vaccines. To better understand the molecular mechanism of action of therapeutic Cancer Peptide vaccines and also to better monitor patients9 immunological response as a predictive biomarker, a fast, sensitive, comprehensive, and quantitative method to characterize T lymphocytes is highly desired. However, TCR repertoire diversity and clonotype follow-up after Cancer vaccination represent a major challenge due to the enormous complexity of the TCR that characterizes individual T cell clones. Here, we demonstrated a new high throughput sequencing method to investigate the detailed genetic profiling of the TCR repertoire of millions of peripheral T lymphocytes from non-small cell lung Cancer (NSCLC) patients who had been treated with Cancer vaccine cocktail of Peptides derived from CDCA1, URLC10, and KIF20A. The new technology of cDNA sequences of TCR α and β chains using next generation DNA sequencer (Ion Torrent Personal Genome Machine (PGM) with 400bp sequencing chemistry) enabled us to assess the comprehensive TCR α and β repertoire information in an unbiased way. We also developed a novel algorithm ‘VDJ decomposition with soft-clipping’ that allowed us to identify the rearranged V-(D)-J regions in both TCR α and β chains, to analyze non-template nucleotides added at the junction sites, and also to determine the exact length and sequence of the complement determining region 3 (CDR3). In total, 16 samples from 5 NSCLC patients with different time points (before and after treatment) were analyzed for both TCR α and β repertoire. We obtained average 239,689 (range: 103,851 - 329,817) VJ identified reads for TCR α sequences and 499,210 (range: 193,753 - 982,040) VDJ identified reads for TCR β sequences. Significant increases of specific TCRβ CDR3 sequences were observed in patients showing stable condition after vaccine treatment. In patient #1 with long stable disease (SD) after treatment, two enriched clones of CASSSLQNIQYF and CASSPSVGLAGVAQKETQYF were present after vaccine treatment, suggesting those clones might represent Peptide-specific cytotoxic T lymphocytes. Similarly, enriched CDR3 clones of CASTVRQKDGYTF and CSVGAYRGETQYF were observed in patient #3 and #5 at SD condition. In conclusion, this newly-developed NGS technology with the novel algorism should contribute to the better understanding of the immune responses in patients treated with immunotherapy. Our approach can also be applied for the investigation of a wide range of immune-related disorders including rejection after organ transplantation. Citation Format: Hua Fang, Rui Yamaguchi, Xiao Liu, Yataro Daigo, Satoru Miyano, Yusuke Nakamura. Quantitative t cell receptor (tcr) repertoire analysis by next-generation sequencing (ngs) in non-small cell lung Cancer patients treated with therapeutic Cancer Peptide vaccines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3568. doi:10.1158/1538-7445.AM2014-3568
Liying Han - One of the best experts on this subject based on the ideXlab platform.
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Phage Display Technology and its Applications in Cancer Immunotherapy.
Anti-cancer agents in medicinal chemistry, 2019Co-Authors: Yicun Wang, Shuohui Gao, Jiayin Lv, Yang Lin, Li Zhou, Liying HanAbstract:Phage display is an effective technology for generation and selection targeting protein for a variety of purpose, which is based on a direct linkage between the displayed protein and the DNA sequence encoding it and utilized in selecting Peptides, improving Peptides affinity and indicating protein-protein interactions. Phage particles displaying Peptide have the potential to apply in the identification of cell-specific targeting molecules, identification of Cancer cell surface biomarkers, identification anti-Cancer Peptide, and the design of Peptide-based antiCancer therapy. Literature searches, reviews and assessments about Phage were performed in this review from PubMed and Medline databases. The phage display technology is an inexpensive method for expressing exogenous Peptides, generating unique Peptides that bind any given target and investigating protein-protein interactions. Due to the powerful ability to insert exogenous gene and display exogenous Peptides on the surface, phages may represent a powerful Peptide delivery system that can be utilized to develop rapid, efficient, safe and inexpensive Cancer therapy methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
