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Neoepitope and cancer

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https://www.readbyqxmd.com/read/29092006/novel-tools-to-assist-neoepitope-targeting-in-personalized-cancer-immunotherapy
#1
S K Saini, N Rekers, S R Hadrup
Current cancer immunotherapy approaches utilize the remarkable surveillance capacity of the human immune system, which is capable of recognizing and eliminating cancer cells based on identification of tumor-associated antigens arising as a consequence of the transformation process. Among these, mutational-derived neoepitopes have proved to be powerful targets for tumor elimination and mutational load has been shown to correlate with the clinical response to treatment with checkpoint inhibitors in many different tumor types...
October 30, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28976134/tumor-protein-53-mutations-mapping-to-its-tertiary-structure-with-in-silico-prediction-of-neoepitopic-vaccine-candidates-in-bone-tumors
#2
Hamid Nawaz Tipu, Abdul Rehman Arshad
Mapping of tp 53 mutations in bone cancers present in COSMIC database to its secondary and tertiary structure with in silico prediction of newly formed HLA binding epitopes as candidates for synthetic peptide vaccine. Mutations in bone cancers present in COSMIC database were listed and manually induced in wt p53 FASTA sequence. Wt p53 secondary structure was predicted. Template identified and tertiary structure of wt p53 was modelled in Cn3D followed by individual mutations mapping onto this model. HLA class I binding affinity was determined for mutated sequences to determine any newly binding peptide sequences...
September 2017: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/28961847/intratumoural-evolutionary-landscape-of-high-risk-prostate-cancer-the-progeny-study-of-genomic-and-immune-parameters
#3
M Linch, G Goh, C Hiley, Y Shanmugabavan, N McGranahan, A Rowan, Y N S Wong, H King, A Furness, A Freeman, J Linares, A Akarca, J Herrero, R Rosenthal, N Harder, G Schmidt, G A Wilson, N J Birkbak, R Mitter, S Dentro, P Cathcart, M Arya, E Johnston, R Scott, M Hung, M Emberton, G Attard, Z Szallasi, S Punwani, S A Quezada, T Marafioti, M Gerlinger, H U Ahmed, C Swanton
Background: Intratumoural heterogeneity (ITH) is well recognised in prostate cancer (PC), but its role in high-risk disease is uncertain. A prospective, single-arm, translational study using targeted multiregion prostate biopsies was carried out to study genomic and T-cell ITH in clinically high-risk PC aiming to identify drivers and potential therapeutic strategies. Patients and methods: Forty-nine men with elevated prostate-specific antigen and multiparametric-magnetic resonance imaging detected PC underwent image-guided multiregion transperineal biopsy...
October 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28954787/mutational-analysis-of-gene-fusions-predicts-novel-mhc-class-i-restricted-t-cell-epitopes-immune-signatures-in-a-subset-of-prostate-cancer
#4
Jennifer L Kalina, David S Neilson, Yen-Yi Lin, Phineas T Hamilton, Alexandra Paige Comber, Emma M H Loy, S Cenk Sahinalp, Colin C Collins, Faraz Hach, Julian J Lum
PURPOSE: Gene fusions are frequently found in prostate cancer and may result in the formation of unique chimeric amino acid sequences (CASQs) that span the breakpoint of two fused gene products. This study evaluated the potential for fusion-derived CASQs to be a source of tumor neoepitopes, and determined their relationship to patterns of immune signatures in prostate cancer patients Experimental Design: A computational strategy was used to identify CASQs and their corresponding predicted MHC class I epitopes using RNA-Seq data from The Cancer Genome Atlas of prostate tumors...
September 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28912897/genomic-analysis-of-tumor-microenvironment-immune-types-across-14-solid-cancer-types-immunotherapeutic-implications
#5
Yu-Pei Chen, Yu Zhang, Jia-Wei Lv, Ying-Qin Li, Ya-Qin Wang, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Yan-Ping Mao, Jing-Ping Yun, Na Liu, Jun Ma
We performed a comprehensive immuno-genomic analysis of tumor microenvironment immune types (TMITs), which is classified into four groups based on PD-L1+CD8A or PD-L1+cytolytic activity (CYT) expression, across a broad spectrum of solid tumors in order to help identify patients who will benefit from anti- PD-1/PD-L1 therapy. The mRNA sequencing data from The Cancer Genome Atlas (TCGA) of 14 solid cancer types representing 6,685 tumor samples was analyzed. TMIT was classified only for those tumor types that both PD-L1 and CD8A/CYT could prefict mutation and/or neoantigen number...
2017: Theranostics
https://www.readbyqxmd.com/read/28854978/the-neoepitope-landscape-in-pediatric-cancers
#6
Ti-Cheng Chang, Robert A Carter, Yongjin Li, Yuxin Li, Hong Wang, Michael N Edmonson, Xiang Chen, Paula Arnold, Terrence L Geiger, Gang Wu, Junmin Peng, Michael Dyer, James R Downing, Douglas R Green, Paul G Thomas, Jinghui Zhang
BACKGROUND: Neoepitopes derived from tumor-specific somatic mutations are promising targets for immunotherapy in childhood cancers. However, the potential for such therapies in targeting these epitopes remains uncertain due to a lack of knowledge of the neoepitope landscape in childhood cancer. Studies to date have focused primarily on missense mutations without exploring gene fusions, which are a major class of oncogenic drivers in pediatric cancer. METHODS: We developed an analytical workflow for identification of putative neoepitopes based on somatic missense mutations and gene fusions using whole-genome sequencing data...
August 31, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28854952/clinical-implications-of-neoepitope-landscapes-for-adult-and-pediatric-cancers
#7
REVIEW
Yang-Yang Feng, Obi L Griffith, Malachi Griffith
Many immunotherapies rely on the presence of neoepitopes derived from somatic mutations that lead to altered peptide sequences. Several studies have now analyzed the neoepitope landscape of different cancer subtypes, predominantly for adult samples, which tend to feature significantly higher mutational burden. However, a new report publishing the first comprehensive analysis of the pediatric neoepitope landscape suggests that immunotherapies could also hold promise for pediatric cancers.See related research article 10...
August 31, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28841418/heterogeneous-tumor-immune-microenvironments-among-differentially-growing-metastases-in-an-ovarian-cancer-patient
#8
Alejandro Jiménez-Sánchez, Danish Memon, Stephane Pourpe, Harini Veeraraghavan, Yanyun Li, Hebert Alberto Vargas, Michael B Gill, Kay J Park, Oliver Zivanovic, Jason Konner, Jacob Ricca, Dmitriy Zamarin, Tyler Walther, Carol Aghajanian, Jedd D Wolchok, Evis Sala, Taha Merghoub, Alexandra Snyder, Martin L Miller
We present an exceptional case of a patient with high-grade serous ovarian cancer, treated with multiple chemotherapy regimens, who exhibited regression of some metastatic lesions with concomitant progression of other lesions during a treatment-free period. Using immunogenomic approaches, we found that progressing metastases were characterized by immune cell exclusion, whereas regressing and stable metastases were infiltrated by CD8(+) and CD4(+) T cells and exhibited oligoclonal expansion of specific T cell subsets...
August 24, 2017: Cell
https://www.readbyqxmd.com/read/28572258/immunotherapy-for-breast-cancer-what-are-we-missing
#9
EDITORIAL
Robert H Vonderheide, Susan M Domchek, Amy S Clark
The recent demonstration of modest single-agent activity of programmed death-ligand 1 (PD-L1) and programmed death receptor-1 (PD-1) antibodies in patients with breast cancer has generated hope that breast cancer can be made amenable to immunotherapy. Depending on the subtype of breast cancer, it is now clear in both primary and metastatic disease that the extent of tumor-infiltrating T cells is not only prognostic for survival but predictive of response to nonimmune, standard therapies. Despite these findings, immune cytolytic activity in spontaneous breast tumors, the burden of nonsynonymous tumor mutations, and the predicted load of neoepitopes-factors linked to response to checkpoint blockade in other malignancies-are all relatively modest in breast cancer compared with melanoma or lung cancer...
June 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28536262/in-silico-and-cell-based-analyses-reveal-strong-divergence-between-prediction-and-observation-of-t-cell-recognized-tumor-antigen-t-cell-epitopes
#10
COMPARATIVE STUDY
Julien Schmidt, Philippe Guillaume, Danijel Dojcinovic, Julia Karbach, George Coukos, Immanuel Luescher
Tumor exomes provide comprehensive information on mutated, overexpressed genes and aberrant splicing, which can be exploited for personalized cancer immunotherapy. Of particular interest are mutated tumor antigen T-cell epitopes, because neoepitope-specific T cells often are tumoricidal. However, identifying tumor-specific T-cell epitopes is a major challenge. A widely used strategy relies on initial prediction of human leukocyte antigen-binding peptides by in silico algorithms, but the predictive power of this approach is unclear...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28533942/hla-a24-ligandome-analysis-of-colon-and-lung-cancer-cells-identifies-a-novel-cancer-testis-antigen-and-a-neoantigen-that-elicits-specific-and-strong-ctl-responses
#11
Vitaly Kochin, Takayuki Kanaseki, Serina Tokita, Sho Miyamoto, Yosuke Shionoya, Yasuhiro Kikuchi, Daichi Morooka, Yoshihiko Hirohashi, Tomohide Tsukahara, Kazue Watanabe, Shingo Toji, Yasuo Kokai, Noriyuki Sato, Toshihiko Torigoe
This study focused on HLA-A24 and comprehensively analyzed the ligandome of colon and lung cancer cells without the use of MHC-binding in silico prediction algorithms. Affinity purification using the antibody specific to HLA-A24 followed by LC-MS/MS sequencing was used to detect peptides, which harbored the known characteristics of HLA-A24 peptides in terms of length and anchor motifs. Ligandome analysis demonstrated the natural presentation of two different types of novel tumor-associated antigens. The ligandome contained a peptide derived from SUV39H2, a gene found to be expressed in a variety of cancers but not in normal tissues (except for the testis)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28303769/neoepitopes-as-cancer-immunotherapy-targets-key-challenges-and-opportunities
#12
REVIEW
Cory A Brennick, Mariam M George, William L Corwin, Pramod K Srivastava, Hakimeh Ebrahimi-Nik
Over the last half century, it has become well established that cancers can elicit a host immune response that can target them with high specificity. Only within the last decade, with the advances in high-throughput gene sequencing and bioinformatics approaches, are we now on the forefront of harnessing the host's immune system to treat cancer. Recently, some strides have been taken toward understanding effective tumor-specific MHC I restricted epitopes or neoepitopes. However, many fundamental questions still remain to be addressed before this therapy can live up to its full clinical potential...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28257957/the-cancer-immunity-cycle-as-rational-design-for-synthetic-cancer-drugs-novel-dc-vaccines-and-car-t-cells
#13
REVIEW
Mohanraj Ramachandran, Anna Dimberg, Magnus Essand
Cell therapy is an advanced form of cancer immunotherapy that has had remarkable clinical progress in the past decade in the search for cure of cancer. Most success has been achieved for chimeric antigen receptor (CAR) T-cells where CAR T-cells targeting CD19 show very high complete response rates for patients with refractory acute B-cell acute lymphoblastic leukemia (ALL) and are close to approval for this indication. CD19 CAR T-cells are also effective against B-cell chronic lymphoblastic leukemia (CLL) and B-cell lymphomas...
August 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28116089/it-s-a-long-way-to-the-top-if-you-want-to-personalize-immunotherapy
#14
EDITORIAL
Sarah Haebe, Oliver Weigert
Harnessing the immune system to attack tumor cells by targeting tumor-associated or -preferably- tumor-specific antigens has emerged as a promising but challenging treatment option for malignant lymphomas. Follicular lymphoma is among the most common lymphomas worldwide and remains incurable for most patients. Considered to be an immunogenic disease it represents an interesting disease entity for various immunotherapeutic approaches. In an article published in the May issue of Clinical Cancer Research, Nielsen and colleagues provided important proof-of-principle data on the immunogenicity of follicular lymphoma that might represent a first step towards personalized adoptive immunotherapies in this disease...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28100240/reactivation-of-dormant-anti-tumor-immunity-a-clinical-perspective-of-therapeutic-immune-checkpoint-modulation
#15
REVIEW
Richard Greil, Evelyn Hutterer, Tanja Nicole Hartmann, Lisa Pleyer
In favor of their outgrowth, cancer cells must resist immune surveillance and edit the immune response. Cancer immunoediting is characterized by fundamental changes in the cellular composition and the inflammatory cytokine profiles in the microenvironment of the primary tumor and metastatic niches, with an ever increasing complexity of interactions between tumor cells and the immune system. Recent data suggest that genetic instability and immunoediting are not necessarily disparate processes. Increasing mutational load may be associated with multiple neoepitopes expressed by the tumor cells and thus increased chances for the immune system to recognize and combat these cells...
January 19, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28007776/immune-cytolytic-activity-stratifies-molecular-subsets-of-human-pancreatic-cancer
#16
David Balli, Andrew J Rech, Ben Z Stanger, Robert H Vonderheide
Purpose: Immunotherapy has the potential to improve the dismal prognosis in pancreatic ductal adenocarcinoma (PDA), but clinical trials, including those with single-agent PD-1 or PD-L1 inhibition, have been disappointing. Our aim was to examine the immune landscape of PDA as it relates to aspects of tumor biology, including neoepitope burden.Experimental Design: We used publicly available expression data from 134 primary resection PDA samples from The Cancer Genome Atlas to stratify patients according to a cytolytic T-cell activity expression index...
December 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27956380/somatic-mutations-and-neoepitope-homology-in-melanomas-treated-with-ctla-4-blockade
#17
Tavi Nathanson, Arun Ahuja, Alexander Rubinsteyn, Bulent Arman Aksoy, Matthew D Hellmann, Diana Miao, Eliezer Van Allen, Taha Merghoub, Jedd D Wolchok, Alexandra Snyder, Jeff Hammerbacher
Immune checkpoint inhibitors are promising treatments for patients with a variety of malignancies. Toward understanding the determinants of response to immune checkpoint inhibitors, it was previously demonstrated that the presence of somatic mutations is associated with benefit from checkpoint inhibition. A hypothesis was posited that neoantigen homology to pathogens may in part explain the link between somatic mutations and response. To further examine this hypothesis, we reanalyzed cancer exome data obtained from our previously published study of 64 melanoma patients treated with CTLA-4 blockade and a new dataset of RNA-Seq data from 24 of these patients...
January 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/27869121/direct-identification-of-clinically-relevant-neoepitopes-presented-on-native-human-melanoma-tissue-by-mass-spectrometry
#18
Michal Bassani-Sternberg, Eva Bräunlein, Richard Klar, Thomas Engleitner, Pavel Sinitcyn, Stefan Audehm, Melanie Straub, Julia Weber, Julia Slotta-Huspenina, Katja Specht, Marc E Martignoni, Angelika Werner, Rüdiger Hein, Dirk H Busch, Christian Peschel, Roland Rad, Jürgen Cox, Matthias Mann, Angela M Krackhardt
Although mutations may represent attractive targets for immunotherapy, direct identification of mutated peptide ligands isolated from human leucocyte antigens (HLA) on the surface of native tumour tissue has so far not been successful. Using advanced mass spectrometry (MS) analysis, we survey the melanoma-associated immunopeptidome to a depth of 95,500 patient-presented peptides. We thereby discover a large spectrum of attractive target antigen candidates including cancer testis antigens and phosphopeptides...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27837020/density-of-immunogenic-antigens-does-not-explain-the-presence-or-absence-of-the-t-cell-inflamed-tumor-microenvironment-in-melanoma
#19
Stefani Spranger, Jason J Luke, Riyue Bao, Yuanyuan Zha, Kyle M Hernandez, Yan Li, Alexander P Gajewski, Jorge Andrade, Thomas F Gajewski
Melanoma metastases can be categorized by gene expression for the presence of a T-cell-inflamed tumor microenvironment, which correlates with clinical efficacy of immunotherapies. T cells frequently recognize mutational antigens corresponding to nonsynonymous somatic mutations (NSSMs), and in some cases shared differentiation or cancer-testis antigens. Therapies are being pursued to trigger immune infiltration into non-T-cell-inflamed tumors in the hope of rendering them immunotherapy responsive. However, whether those tumors express antigens capable of T-cell recognition has not been explored...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27832200/a-platform-for-designing-genome-based-personalized-immunotherapy-or-vaccine-against-cancer
#20
Sudheer Gupta, Kumardeep Chaudhary, Sandeep Kumar Dhanda, Rahul Kumar, Shailesh Kumar, Manika Sehgal, Gandharva Nagpal, Gajendra P S Raghava
Due to advancement in sequencing technology, genomes of thousands of cancer tissues or cell-lines have been sequenced. Identification of cancer-specific epitopes or neoepitopes from cancer genomes is one of the major challenges in the field of immunotherapy or vaccine development. This paper describes a platform Cancertope, developed for designing genome-based immunotherapy or vaccine against a cancer cell. Broadly, the integrated resources on this platform are apportioned into three precise sections. First section explains a cancer-specific database of neoepitopes generated from genome of 905 cancer cell lines...
2016: PloS One
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