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https://www.readbyqxmd.com/read/28453704/genomic-characterization-of-her2-positive-breast-cancer-and-response-to-neoadjuvant-trastuzumab-and-chemotherapy-results-from-the-acosog-z1041-alliance-trial
#1
R Lesurf, O L Griffith, M Griffith, J Hundal, L Trani, M A Watson, R Aft, M J Ellis, D Ota, V J Suman, F Meric-Bernstam, A M Leitch, J C Boughey, G Unzeitig, A U Buzdar, K K Hunt, E R Mardis
Background: HER2 (ERBB2) gene amplification and its corresponding overexpression are present in 15-30% of invasive breast cancers. While HER2-targeted agents are effective treatments, resistance remains a major cause of death. The American College of Surgeons Oncology Group Z1041 trial (NCT00513292) was designed to compare the pathologic complete response (pCR) rate of distinct regimens of neoadjuvant chemotherapy and trastuzumab, but ultimately identified no difference. Patients and methods: In supplement to tissues from 37 Z1041 cases, 11 similarly treated cases were obtained from a single institution study (NCT00353483)...
May 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28431188/t-cell-receptor-%C3%AE-chain-repertoire-analysis-reveals-the-association-between-neoantigens-and-tumour-infiltrating-lymphocytes-in-multifocal-papillary-thyroid-carcinoma
#2
Zheming Lu, Chaoting Zhang, Jindong Sheng, Jing Shen, Baoguo Liu
To explore whether a few non-synonymous somatic mutations could induce activation and proliferation of neoantigen-specific tumour-infiltrating lymphocytes (TILs) in tumours with low mutation rates, we analysed a patient with multifocal papillary thyroid carcinoma (seven non-contiguous cancer foci) to investigate the relationship between neoantigens and TILs. These seven foci had a few or no non-synonymous somatic mutations; moreover, multiple loci had similar or different spectra of mutations. We used high-throughput sequencing of the rearranged genes in T cell receptor β-chain (TCRβ) to reveal the basic characteristics of T cells in seven tumour foci and matched adjacent normal tissue...
April 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28428277/immune-gene-expression-is-associated-with-genomic-aberrations-in-breast-cancer
#3
Anton Safonov, Tingting Jiang, Giampaolo Bianchini, Balázs Győrffy, Thomas Karn, Christos Hatzis, Lajos Pusztai
The presence of tumor-infiltrating lymphocytes (TIL) is a favorable prognostic factor in breast cancer, but what drives immune infiltration remains unknown. Here we examine if clonal heterogeneity, total mutation load, neoantigen load, copy number variations (CNV), gene- or pathway-level somatic mutations, or germline polymorphisms (SNP) are associated with immune metagene expression in breast cancer subtypes. Thirteen published immune metagenes correlated separately with genomic metrics in the 3 major breast cancer subtypes...
April 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28423700/hla-class-i-loss-in-metachronous-metastases-prevents-continuous-t-cell-recognition-of-mutated-neoantigens-in-a-human-melanoma-model
#4
Barbara Schrörs, Silke Lübcke, Volker Lennerz, Martina Fatho, Anne Bicker, Catherine Wölfel, Patrick Derigs, Thomas Hankeln, Dirk Schadendorf, Annette Paschen, Thomas Wölfel
T lymphocytes against tumor-specific mutated neoantigens can induce tumor regression. Also, the size of the immunogenic cancer mutanome is supposed to correlate with the clinical efficacy of checkpoint inhibition. Herein, we studied the susceptibility of tumor cell lines from lymph node metastases occurring in a melanoma patient over several years towards blood-derived, neoantigen-specific CD8+ T cells. In contrast to a cell line established during early stage III disease, all cell lines generated at later time points from stage IV metastases exhibited partial or complete loss of HLA class I expression...
March 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410302/tumor-infiltrating-lymphocyte-therapy-and-neoantigens
#5
Paul F Robbins
The adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes has been shown to be effective at mediating tumor regression in more than half of patients with metastatic melanoma and in mediating long-term complete regression in approximately one fourth of all patients with this cancer. The success of this approach in patients with cholangiocarcinoma and colon cancer supports efforts to expand ACT therapies to treatment of patients bearing a wide array of cancer types. Recent improvements in deep sequencing of the patient cancers, combined with extensive immunological testing of autologous tumor-infiltrating lymphocytes, indicate that T cells targeting epitopes arising from nonsynonymous somatic mutations, termed neoantigens, play important roles in mediating many of the effective cancer immunotherapies seen in response to ACT...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28410301/dendritic-cell-strategies-for-eliciting-mutation-derived-tumor-antigen-responses-in-patients
#6
Sreekumar Balan, John Finnigan, Nina Bhardwaj
Dendritic cells (DCs) are equipped for sensing danger signals and capturing, processing, and presenting antigens to naive or effector cells and are critical in inducing humoral and adaptive immunity. Successful vaccinations are those that activate DCs to elicit both cellular and humoral responses, as well as long-lasting memory response against the target of interest. Recently, it has become apparent that tumor cells can provide new sources of antigens through nonsynonymous mutations or frame-shift mutations, leading to potentially hundreds of mutation-derived tumor antigens (MTAs) or neoantigens...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28410300/applied-cancer-immunogenomics-leveraging-neoantigen-discovery-in-glioblastoma
#7
Tanner M Johanns, Gavin P Dunn
Glioblastoma (GBM) remains a significant cause of cancer-related mortality in pediatric and adult patients with limited treatment options. Immunotherapy represents a promising new therapeutic approach in many solid and hematologic malignancies, including GBM, although only a subset of patients responds clinically. Thus, current efforts are focused on identifying patients most likely to benefit from immune-based therapies. The cancer immunogenomics approach identifies candidate neoantigens from genomics information and represents a potentially exciting new space in precision neuro-oncology...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28410296/neoantigen-discovery-in-human-cancers
#8
Elaine R Mardis
Cancer is caused by alterations to DNA that ultimately are translated into altered proteins with unique amino acid sequences when compared with their counterparts in normal cells. By inference, these altered proteins have the potential to elicit immune responses such as T-cell recognition, if properly presented by the immune system following protein degradation and major histocompatibility complex binding. Historically, identifying tumor-specific mutant antigens was painstaking work that involved molecular cloning and immune screening...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28408606/landscape-of-immunogenic-tumor-antigens-in-successful-immunotherapy-of-virally-induced-epithelial-cancer
#9
Sanja Stevanović, Anna Pasetto, Sarah R Helman, Jared J Gartner, Todd D Prickett, Bryan Howie, Harlan S Robins, Paul F Robbins, Christopher A Klebanoff, Steven A Rosenberg, Christian S Hinrichs
Immunotherapy has clinical activity in certain virally associated cancers. However, the tumor antigens targeted in successful treatments remain poorly defined. We used a personalized immunogenomic approach to elucidate the global landscape of antitumor T cell responses in complete regression of human papillomavirus-associated metastatic cervical cancer after tumor-infiltrating adoptive T cell therapy. Remarkably, immunodominant T cell reactivities were directed against mutated neoantigens or a cancer germline antigen, rather than canonical viral antigens...
April 14, 2017: Science
https://www.readbyqxmd.com/read/28405493/hla-class-i-restricted-myd88-l265p-derived-peptides-as-specific-targets-for-lymphoma-immunotherapy
#10
Annika Nelde, Juliane Sarah Walz, Daniel Johannes Kowalewski, Heiko Schuster, Olaf-Oliver Wolz, Janet Kerstin Peper, Yamel Cardona Gloria, Anton W Langerak, Alice F Muggen, Rainer Claus, Irina Bonzheim, Falko Fend, Helmut Rainer Salih, Lothar Kanz, Hans-Georg Rammensee, Stefan Stevanović, Alexander N R Weber
Genome sequencing has uncovered an array of recurring somatic mutations in different non-Hodgkin lymphoma (NHL) subtypes. If affecting protein-coding regions, such mutations may yield mutation-derived peptides that may be presented by HLA class I proteins and recognized by cytotoxic T cells. A recurring somatic and oncogenic driver mutation of the Toll-like receptor adaptor protein MYD88, Leu265Pro (L265P) was identified in up to 90% of different NHL subtype patients. We therefore screened the potential of MYD88(L265P)-derived peptides to elicit cytotoxic T cell responses as tumor-specific neoantigens...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28404974/tumor-immunotherapy-drug-induced-neoantigens-xenogenization-and-immune-checkpoint-inhibitors
#11
Ornella Franzese, Francesco Torino, Maria Pia Fuggetta, Angelo Aquino, Mario Roselli, Enzo Bonmassar, Anna Giuliani, Stefania D'Atri
More than 40 years ago, we discovered that novel transplantation antigens can be induced in vivo or in vitro by treating murine leukemia with dacarbazine. Years later, this phenomenon that we called "Chemical Xenogenization" (CX) and more recently, "Drug-Induced Xenogenization" (DIX), was reproduced by Thierry Boon with a mutagenic/carcinogenic compound (i.e. N-methyl-N'-nitro-N-nitrosoguanidine). In both cases, the molecular bases of DIX rely on mutagenesis induced by methyl adducts to oxygen-6 of DNA guanine...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403580/correction-membrane-associated-cancer-oocyte-neoantigen-sas1b-ovastacin-is-a-candidate-immunotherapeutic-target-for-uterine-tumors
#12
Eusebio S Pires, Ryan S D'Souza, Marisa A Needham, Austin K Herr, Amir A Jazaeri, Hui Li, Mark H Stoler, Kiley L Anderson-Knapp, Theodore Thomas, Arabinda Mandal, Alain Gougeon, Charles J Flickinger, David E Bruns, Brian A Pollok, John C Herr
No abstract text is available yet for this article.
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389595/cancer-immunogenomics-computational-neoantigen-identification-and-vaccine-design
#13
Jasreet Hundal, Christopher A Miller, Malachi Griffith, Obi L Griffith, Jason Walker, Susanna Kiwala, Aaron Graubert, Joshua McMichael, Adam Coffman, Elaine R Mardis
The application of modern high-throughput genomics to the study of cancer genomes has exploded in the past few years, yielding unanticipated insights into the myriad and complex combinations of genomic alterations that lead to the development of cancers. Coincident with these genomic approaches have been computational analyses that are capable of multiplex evaluations of genomic data toward specific therapeutic end points. One such approach is called "immunogenomics" and is now being developed to interpret protein-altering changes in cancer cells in the context of predicted preferential binding of these altered peptides by the patient's immune molecules, specifically human leukocyte antigen (HLA) class I and II proteins...
April 7, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28389576/integrated-profiling-uncovers-lymphoma-immunoglobulin-neoantigens
#14
(no author information available yet)
CD4(+) T cells specific for immunoglobulin-derived neoantigens target autologous lymphoma cells.
April 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28382562/biomarkers-to-predict-prognosis-and-response-to-checkpoint-inhibitors
#15
REVIEW
Takeshi Yuasa, Hitoshi Masuda, Shinya Yamamoto, Noboru Numao, Junji Yonese
Nivolumab is a fully human immunoglobulin (Ig) G4 antibody that selectively inhibits the programmed death 1 (PD-1) immune checkpoint molecule, and has recently been launched for the treatment of renal cell cancer (RCC) in Japan. Based on its promising anti-tumor efficacy and manageable safety profile demonstrated in the phase III Checkmate 025 trial, nivolumab therapy is rapidly being introduced in metastatic RCC clinical practice. The phase Ia study of atezolizumab, which is a humanized anti-PD-ligand 1 (PD-L1) monoclonal IgG1 antibody, also demonstrated excellent treatment results...
April 5, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28379630/uv-induced-somatic-mutations-elicit-a-functional-t-cell-response-in-the-yummer1-7-mouse-melanoma-model
#16
Jake Wang, Curtis Jamison Perry, Katrina Meeth, Durga Thakral, William Damsky, Goran Micevic, Susan Kaech, Kim Blenman, Marcus Bosenberg
Human melanomas exhibit relatively high somatic mutation burden compared to other malignancies. These somatic mutations may produce neoantigens that are recognized by the immune system, leading to an anti-tumor response. By irradiating a parental mouse melanoma cell line carrying three driver mutations with UVB and expanding a single cell clone, we generated a mutagenized model that exhibits high somatic mutation burden. When inoculated at low cell numbers in immunocompetent C57BL/6J mice, YUMMER1.7 (YUMM Exposed to Radiation) regresses after a brief period of growth...
April 5, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28371614/hypermutations-in-gliomas-a-potential-immunotherapy-target
#17
Gaetano Finocchiaro, Tiziana Langella, Cristina Corbetta, Serena Pellegatta
Checkpoint inhibitors, like ipilimumab, nivolumab, and pembrolizumab, have provided a breakthrough in cancer immunotherapy, such as in the treatment of melanoma and colorectal and lung cancer. The close relationship between the number of mutations (mutational load) and the response to checkpoint immunotherapy has been convincingly demonstrated in these cancers. Hypermutations in tumors are caused by environmental factors, like UV radiations or cigarette smoking, or by germinal mutations affecting genes of the Mismatch Repair (MMR) machinery, as in the Lynch syndrome...
February 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28369971/red-blood-cells-derived-from-whole-blood-treated-with-riboflavin-and-ultraviolet-light-maintain-adequate-survival-in-vivo-after-21-days-of-storage
#18
Jose A Cancelas, Sherrill J Slichter, Neeta Rugg, P Gayle Pratt, Shawnagay Nestheide, Jill Corson, Esther Pellham, Marty Huntington, Raymond P Goodrich
BACKGROUND: Pathogen reduction (PR) of whole blood (WB) may increase blood safety when applied before component separation. This study evaluates the in vivo performance of red blood cells (RBCs) derived from WB treated with the riboflavin and ultraviolet (UV) light PR (Mirasol) system. STUDY DESIGN AND METHODS: This was a prospective, two-center, single-blind, randomized, two-period, crossover clinical trial designed to evaluate autologous (51) Cr/(99m) Tc-radiolabeled recovery and survival of RBCs derived from Mirasol-treated WB compared to untreated WB...
May 2017: Transfusion
https://www.readbyqxmd.com/read/28366678/harnessing-the-immunotherapy-revolution-for-the-treatment-of-childhood-cancers
#19
REVIEW
Robbie G Majzner, Sabine Heitzeneder, Crystal L Mackall
Cancer immunotherapies can be classified into agents that amplify natural immune responses (e.g., checkpoint inhibitors) versus synthetic immunotherapies designed to initiate new responses (e.g., monoclonal antibodies [mAbs], chimeric antigen receptors [CARs]). Checkpoint inhibitors mediate unprecedented benefit in some adult cancers, but have not demonstrated significant activity in pediatric cancers, likely due their paucity of neoantigens. In contrast, synthetic immunotherapies such as mAbs and CAR T cells demonstrate impressive effects against childhood cancers...
April 10, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28363643/genetic-features-of-aflatoxin-associated-hepatocellular-carcinomas
#20
Weilong Zhang, Huan He, Mengya Zang, Qifeng Wu, Hong Zhao, Ling-Ling Lu, Peiqing Ma, Hongwei Zheng, Nengjin Wang, Ying Zhang, Siyuan He, Xiaoyan Chen, Zhiyuan Wu, Xiaoyue Wang, Jianqiang Cai, Zhihua Liu, Zongtang Sun, Yi-Xin Zeng, Chunfeng Qu, Yuchen Jiao
BACKGROUND & AIMS: Dietary exposure to aflatoxin is an important risk factor for hepatocellular carcinoma (HCC). However, little is known about the genomic features and mutations of aflatoxin-associated HCCs compared with HCCs not associated with aflatoxin exposure. We investigated the genetic features of aflatoxin-associated HCC that can be used to differentiate them from HCCs not associated with this carcinogen. METHODS: We obtained HCC tumor tissues and matched non-tumor liver tissues from 49 patients, collected from 1990 through 2016, at the Qidong Liver Cancer Hospital Institute in China-a high-risk region for aflatoxin exposure (38...
March 28, 2017: Gastroenterology
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