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Cancer neoantigens

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https://www.readbyqxmd.com/read/29456538/an-uncoupling-of-canonical-phenotypic-markers-and-functional-potency-of-ex-vivo-expanded-natural-killer-cells
#1
Nicole A P Lieberman, Kole DeGolier, Kristen Haberthur, Harrison Chinn, Kara W Moyes, Myriam N Bouchlaka, Kirsti L Walker, Christian M Capitini, Courtney A Crane
Recent advances in cellular therapies for patients with cancer, including checkpoint blockade and ex vivo -expanded, tumor-specific T cells, have demonstrated that targeting the immune system is a powerful approach to the elimination of tumor cells. Clinical efforts have also demonstrated limitations, however, including the potential for tumor cell antigenic drift and neoantigen formation, which promote tumor escape and recurrence, as well as rapid onset of T cell exhaustion in vivo . These findings suggest that antigen unrestricted cells, such as natural killer (NK) cells, may be beneficial for use as an alternative to or in combination with T cell based approaches...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29440180/resistance-promoting-effects-of-ependymoma-treatment-revealed-through-genomic-analysis-of-multiple-recurrences-in-a-single-patient
#2
Christopher A Miller, Sonika Dahiya, Tiandao Li, Robert Fulton, Matthew D Smyth, Gavin P Dunn, Joshua B Rubin, Elaine R Mardis
BACKGROUND: As in other brain tumors, multiple recurrences after complete resection and irradiation of supratentorial ependymoma are common and frequently result in patient death. This standard-of-care treatment was established in the pre-genomic era without the ability to evaluate the effect that mutagenic therapies may exert on tumor evolution and in promoting resistance, recurrence, and death. We seized a rare opportunity to characterize treatment effects and the evolution of a single patient's ependymoma across four recurrences after different therapies...
February 13, 2018: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/29439670/phase-i-study-of-an-active-immunotherapy-for-asymptomatic-phase-lymphoplasmacytic-lymphoma-with-dna-vaccines-encoding-antigen-chemokine-fusion-study-protocol
#3
Sheeba K Thomas, Soung-Chul Cha, D Lynne Smith, Kun Hwa Kim, Sapna R Parshottam, Sheetal Rao, Michael Popescu, Vincent Y Lee, Sattva S Neelapu, Larry W Kwak
BACKGROUND: There is now a renewed interest in cancer vaccines. Patients responding to immune checkpoint blockade usually bear tumors that are heavily infiltrated by T cells and express a high load of neoantigens, indicating that the immune system is involved in the therapeutic effect of these agents; this finding strongly supports the use of cancer vaccine strategies. Lymphoplasmacytic lymphoma (LPL) is a low grade, incurable disease featuring an abnormal proliferation of Immunoglobulin (Ig)-producing malignant cells...
February 13, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29432557/epigenetic-modifiers-as-new-immunomodulatory-therapies-in-solid-tumours
#4
S Aspeslagh, D Morel, J-C Soria, S Postel-Vinay
Background: Immune therapies have revolutionized cancer treatment over the last few years by allowing improvements in overall survival. However, the majority of patients is still primary or secondary resistant to such therapies, and enhancing sensitivity to immune therapies is therefore crucial to improve patient outcome. Several recent lines of evidence suggest that epigenetic modifiers have intrinsic immunomodulatory properties, which could be of therapeutic interest. Material and Methods: We reviewed preclinical evidence and clinical studies which describe or exploit immunomodulatory properties of epigenetic agents...
February 7, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29424427/three-molecular-pathways-model-colorectal-carcinogenesis-in-lynch-syndrome
#5
Aysel Ahadova, Richard Gallon, Johannes Gebert, Alexej Ballhausen, Volker Endris, Martina Kirchner, Albrecht Stenzinger, John Burn, Magnus von Knebel Doeberitz, Hendrik Bläker, Matthias Kloor
Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR) genes. MMR deficiency has long been regarded as a secondary event in the pathogenesis of Lynch syndrome colorectal cancers. Recently, this concept has been challenged by the discovery of MMR-deficient crypt foci in the normal mucosa. We aimed to reconstruct colorectal carcinogenesis in Lynch syndrome by collecting molecular and histology evidence from Lynch syndrome adenomas and carcinomas. We determined the frequency of MMR deficiency in adenomas from Lynch syndrome mutation carriers by immunohistochemistry and by systematic literature analysis...
February 9, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29423108/cancer-immunogenomic-approach-to-neoantigen-discovery-in-a-checkpoint-blockade-responsive-murine-model-of-oral-cavity-squamous-cell-carcinoma
#6
Paul Zolkind, Dariusz Przybylski, Nemanja Marjanovic, Lan Nguyen, Tianxiang Lin, Tanner Johanns, Anton Alexandrov, Liye Zhou, Clint T Allen, Alexander P Miceli, Robert D Schreiber, Maxim Artyomov, Gavin P Dunn, Ravindra Uppaluri
Head and neck squamous cell carcinomas (HNSCC) are an ideal immunotherapy target due to their high mutation burden and frequent infiltration with lymphocytes. Preclinical models to investigate targeted and combination therapies as well as defining biomarkers to guide treatment represent an important need in the field. Immunogenomics approaches have illuminated the role of mutation-derived tumor neoantigens as potential biomarkers of response to checkpoint blockade as well as representing therapeutic vaccines...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29416628/exome-sequencing-reveals-aberrant-signalling-pathways-as-hallmark-of-treatment-naive-anal-squamous-cell-carcinoma
#7
Wulfran Cacheux, Virginie Dangles-Marie, Etienne Rouleau, Julien Lazartigues, Elodie Girard, Adrien Briaux, Pascale Mariani, Sophie Richon, Sophie Vacher, Bruno Buecher, Marion Richard-Molard, Emmanuelle Jeannot, Nicolas Servant, Fereshteh Farkhondeh, Odette Mariani, Thomas Rio-Frio, Sergio Roman-Roman, Emmanuel Mitry, Ivan Bieche, Astrid Lièvre
Anal squamous cell carcinomas (ASCC) are rare tumours in humans. The etiological role of HPV infection is now well established but little is known about the molecular landscape and signalling pathways involved in the pathogenesis of this cancer. Here we report the results from a whole exome sequencing of a homogeneous group of 20 treatment-naive ASCC. A total of 2422 somatic single nucleotide variations (SNV) were found, with an overall moderate rate of somatic mutations per tumour (median: 105 relevant SNV per tumour) but a high mutational load in 3 tumours...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29413421/inflammatory-reprogramming-with-ido1-inhibitors-turning-immunologically-unresponsive-cold-tumors-hot
#8
REVIEW
George C Prendergast, Arpita Mondal, Souvik Dey, Lisa D Laury-Kleintop, Alexander J Muller
We discuss how small-molecule inhibitors of the tryptophan (Trp) catabolic enzyme indoleamine 2,3-dioxygenase (IDO) represent a vanguard of new immunometabolic adjuvants to safely enhance the efficacy of cancer immunotherapy, radiotherapy, or 'immunogenic' chemotherapy by leveraging responses to tumor neoantigens. IDO inhibitors re-program inflammatory processes to help clear tumors by blunting tumor neovascularization and restoring immunosurveillance. Studies of regulatory and effector pathways illuminate IDO as an inflammatory modifier...
January 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29409514/immune-monitoring-and-tcr-sequencing-of-cd4-t-cells-in-a-long-term-responsive-patient-with-metastasized-pancreatic-ductal-carcinoma-treated-with-individualized-neoepitope-derived-multipeptide-vaccines-a-case-report
#9
Katja Sonntag, Hisayoshi Hashimoto, Matthias Eyrich, Moritz Menzel, Max Schubach, Dennis Döcker, Florian Battke, Carolina Courage, Helmut Lambertz, Rupert Handgretinger, Saskia Biskup, Karin Schilbach
BACKGROUND: Cancer vaccines can effectively establish clinically relevant tumor immunity. Novel sequencing approaches rapidly identify the mutational fingerprint of tumors, thus allowing to generate personalized tumor vaccines within a few weeks from diagnosis. Here, we report the case of a 62-year-old patient receiving a four-peptide-vaccine targeting the two sole mutations of his pancreatic tumor, identified via exome sequencing. METHODS: Vaccination started during chemotherapy in second complete remission and continued monthly thereafter...
February 6, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29407608/therapeutic-cancer-vaccines-from-initial-findings-to-prospects
#10
REVIEW
Qian Song, Cheng-Dong Zhang, Xiang-Hua Wu
With the approval of the first therapeutic cancer vaccine by US Food and Drug Administration, numerous therapeutic cancer vaccines have been under clinical trials with an inspiring antitumor immune response in cancer patients. Though there is no therapeutic cancer vaccine showing clinical efficacy in phase III trials, recent advances in personalized cancer vaccine based on neoantigens have emerged as an efficient way to induce tumor regression. In this review, we discuss the selection methods of tumor specific antigen and mainly focus on the development of therapeutic cancer vaccine strategies...
January 30, 2018: Immunology Letters
https://www.readbyqxmd.com/read/29403496/recent-advances-in-targeting-cd8-t-cell-immunity-for-more-effective-cancer-immunotherapy
#11
REVIEW
Aurélie Durgeau, Yasemin Virk, Stéphanie Corgnac, Fathia Mami-Chouaib
Recent advances in cancer treatment have emerged from new immunotherapies targeting T-cell inhibitory receptors, including cytotoxic T-lymphocyte associated antigen (CTLA)-4 and programmed cell death (PD)-1. In this context, anti-CTLA-4 and anti-PD-1 monoclonal antibodies have demonstrated survival benefits in numerous cancers, including melanoma and non-small-cell lung carcinoma. PD-1-expressing CD8+ T lymphocytes appear to play a major role in the response to these immune checkpoint inhibitors (ICI). Cytotoxic T lymphocytes (CTL) eliminate malignant cells through recognition by the T-cell receptor (TCR) of specific antigenic peptides presented on the surface of cancer cells by major histocompatibility complex class I/beta-2-microglobulin complexes, and through killing of target cells, mainly by releasing the content of secretory lysosomes containing perforin and granzyme B...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29391594/contraction-of-t-cell-richness-in-lung-cancer-brain-metastases
#12
Aaron S Mansfield, Hongzheng Ren, Shari Sutor, Vivekananda Sarangi, Asha Nair, Jaime Davila, Laura R Elsbernd, Julia B Udell, Roxana S Dronca, Sean Park, Svetomir N Markovic, Zhifu Sun, Kevin C Halling, Wendy K Nevala, Marie Christine Aubry, Haidong Dong, Jin Jen
Very little is known about how the adaptive immune system responds to clonal evolution and tumor heterogeneity in non-small cell lung cancer. We profiled the T-cell receptor β complementarity determining region 3 in 20 patients with fully resected non-small cell lung cancer primary lesions and paired brain metastases. We characterized the richness, abundance and overlap of T cell clones between pairs, in addition to the tumor mutation burden and predicted neoantigens. We found a significant contraction in the number of unique T cell clones in brain metastases compared to paired primary cancers...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29381830/t-cell-cross-reactivity-may-explain-the-large-variation-in-how-patients-respond-to-checkpoint-inhibitors
#13
REVIEW
Mouldy Sioud
The therapeutic use of the immune system to specifically attack tumors has been a longstanding vision among tumour immunologists. Recently the use of checkpoint inhibitors to turn-off immunosuppressive signals has proven to be effective in enhancing T-cell reactivity against patient-specific neoantigens, resulting from somatic mutations. Several of the identified T-cell epitopes share similarity with common bacterial and viral antigens, suggesting the involvement of pre-existing antimicrobial memory T cells in rapid and durable tumour regression seen in some patients...
January 30, 2018: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29361136/differential-binding-affinity-of-mutated-peptides-for-mhc-class-i-is-a-predictor-of-survival-in-advanced-lung-cancer-and-melanoma
#14
E Ghorani, R Rosenthal, N McGranahan, J L Reading, M Lynch, K S Peggs, C Swanton, S A Quezada
Background: Cancer mutations generate novel (neo-)peptides recognised by T cells, but the determinants of recognition are not well characterised. The difference in predicted class I major histocompatibility complex (MHC-I) binding affinity between wild-type and corresponding mutant peptides (differential agretopicity index; DAI) may reflect clinically relevant cancer peptide immunogenicity. Our aim was to explore the relationship between DAI, measures of immune infiltration and patient outcomes in advanced cancer...
January 1, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29360924/neopepsee-accurate-genome-level-prediction-of-neoantigens-by-harnessing-sequence-and-amino-acid-immunogenicity-information
#15
S Kim, H S Kim, E Kim, M G Lee, E Shin, S Paik, S Kim
Background: Tumor-specific mutations form novel immunogenic peptides called neoantigens. Neoantigens can be used as a biomarker predicting patient response to cancer immunotherapy. Although a predicted binding affinity (IC50) between peptide and major histocompatibility complex class I (MHC-I) is currently used for neoantigen prediction, large number of false-positives exist. Materials and methods: We developed Neopepsee, a machine learning-based neoantigen prediction program for next-generation sequencing data...
January 19, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29360643/tumor-infiltrating-brafv600e-specific-cd4-t-cells-correlated-with-complete-clinical-response-in-melanoma
#16
Joshua R Veatch, Sylvia M Lee, Matthew Fitzgibbon, I-Ting Chow, Brenda Jesernig, Thomas Schmitt, Ying Ying Kong, Julia Kargl, A McGarry Houghton, John A Thompson, Martin McIntosh, William W Kwok, Stanley R Riddell
T cells specific for neoantigens encoded by mutated genes in cancers are increasingly recognized as mediators of tumor destruction after immune checkpoint inhibitor therapy or adoptive cell transfer. Unfortunately, most neoantigens result from random mutations and are patient specific, and some cancers contain few mutations to serve as potential antigens. We describe a patient with stage IV acral melanoma who obtained a complete response following adoptive transfer of tumor infiltrating lymphocytes (TIL). Tumor exome sequencing surprisingly revealed less than 30 somatic mutations, including oncogenic BRAF V600E...
January 23, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29357823/chemotherapy-weakly-contributes-to-predicted-neoantigen-expression-in-ovarian-cancer
#17
Timothy O'Donnell, Elizabeth L Christie, Arun Ahuja, Jacqueline Buros, B Arman Aksoy, David D L Bowtell, Alexandra Snyder, Jeff Hammerbacher
BACKGROUND: Patients with highly mutated tumors, such as melanoma or smoking-related lung cancer, have higher rates of response to immune checkpoint blockade therapy, perhaps due to increased neoantigen expression. Many chemotherapies including platinum compounds are known to be mutagenic, but the impact of standard treatment protocols on mutational burden and resulting neoantigen expression in most human cancers is unknown. METHODS: We sought to quantify the effect of chemotherapy treatment on computationally predicted neoantigen expression for high grade serous ovarian carcinoma patients enrolled in the Australian Ovarian Cancer Study...
January 22, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29333661/nanocage-therapeutics-prevailing-phagocytosis-and-immunogenic-cell-death-awakens-immunity-against-cancer
#18
Eun Jung Lee, Gi-Hoon Nam, Na Kyeong Lee, Minwoo Kih, Eunee Koh, Yoon Kyoung Kim, Yeonsun Hong, Soyoun Kim, Seung-Yoon Park, Cherlhyun Jeong, Yoosoo Yang, In-San Kim
A growing appreciation of the relationship between the immune system and the tumorigenesis has led to the development of strategies aimed at "re-editing" the immune system to kill tumors. Here, a novel tactic is reported for overcoming the activation-energy threshold of the immunosuppressive tumor microenvironment and mediating the delivery and presentation of tumor neoantigens to the host's immune system. This nature-derived nanocage not only efficiently presents ligands that enhance cancer cell phagocytosis, but also delivers drugs that induce immunogenic cancer cell death...
January 15, 2018: Advanced Materials
https://www.readbyqxmd.com/read/29325699/co-delivery-of-tumor-antigen-and-dual-toll-like-receptor-ligands-into-dendritic-cell-by-silicon-microparticle-enables-efficient-immunotherapy-against-melanoma
#19
Motao Zhu, Xilai Ding, Ruifang Zhao, Xuewu Liu, Haifa Shen, Chunmei Cai, Mauro Ferrari, Helen Y Wang, Rong-Fu Wang
Despite the importance and promise of cancer vaccines for broader prevention and treatment of cancer, limited clinical responses are observed, suggesting that key rational designs are required for inducing potent immune responses against cancer. Here we report a mesoporous silicon vector (MSV) as a multi-functional microparticle for formulating an efficient cancer vaccine composed of B16 melanoma derived-tyrosinase related protein 2 (TRP2) peptide and dual toll-like receptor (TLR) agonists. We demonstrated that MSV microparticles protected the peptide from rapid degradation for prolonged antigen presentation to immune cells...
January 8, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29317775/pancreatic-cancer-next-generation-algorithms-for-neoantigen-selection
#20
Alexander Hopkins, Elizabeth Jaffee
No abstract text is available yet for this article.
January 10, 2018: Nature Reviews. Gastroenterology & Hepatology
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