DOCSLIB.ORG

Modelling Vaccination Schedules for a Cancer Immunoprevention Vaccine Santo Motta1, Filippo Castiglione2, Pierluigi Lollini3 and Francesco Pappalardo*1,4

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Modelling Vaccination Schedules for a Cancer Immunoprevention Vaccine Santo Motta1, Filippo Castiglione2, Pierluigi Lollini3 and Francesco Pappalardo*1,4 Immunome Research BioMed Central Research Open Access Modelling vaccination schedules for a cancer immunoprevention vaccine Santo Motta1, Filippo Castiglione2, Pierluigi Lollini3 and Francesco Pappalardo*1,4 Address: 1Department of Mathematics and Computer Science, University of Catania, Catania, Italy, 2Sezione di Cancerologia, Dipartimento di Patologia Sperimentale, University of Bologna, and Centro Interdipartimentale di Ricerche sul Cancro "Giorgio Prodi", Italy, 3Istituto per le Applicazioni del Calcolo, Consiglio Nazionale delle Ricerche, Roma, Italy and 4Faculty of Pharmacy, University of Catania, Italy Email: Santo Motta - [email protected]; Filippo Castiglione - [email protected]; Pierluigi Lollini - [email protected]; Francesco Pappalardo* - [email protected] * Corresponding author Published: 07 October 2005 Received: 09 June 2005 Accepted: 07 October 2005 Immunome Research 2005, 1:5 doi:10.1186/1745-7580-1-5 This article is available from: http://www.immunome-research.com/content/1/1/5 © 2005 Motta et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract We present a systematic approach to search for an effective vaccination schedule using mathematical computerized models. Our study is based on our previous model that simulates the cancer vs immune system competition activated by tumor vaccine. This model accurately reproduces in-vivo experiments results on HER-2/neu mice treated with the immuno-prevention cancer vaccine (Triplex) for mammary carcinoma. In vivo experiments have shown the effectiveness of Triplex vaccine in protection of mice from mammary carcinoma. The full protection was conferred using chronic (prophylactic) vaccination protocol while therapeutic vaccination was less effcient. In the present paper we use the computer simulations to systematically search for a vaccination schedule which prevents solid tumor formation. The strategy we used for defining a successful vaccination schedule is to control the number of cancer cells with vaccination cycles. We found that, applying the vaccination scheme used in in-vivo experiments, the number of vaccine injections can be reduced roughly by 30%. 1 Introduction scopic tumors, but are ineffective against established, Tumor immunologists have long sought ways to turn large tumor masses. A similar situation is found in infec- experimental results into effective therapies for human tious immunity: prophylactic vaccines protect millions of cancer patients. The best results so far are provided by individuals worldwide from pathogens, whereas thera- using various monoclonal antibodies directed against peutic vaccines are mostly ineffective. Such results led tumor cells, which won approval from regulatory agencies some tumor immunologists to the idea that the effort and entered clinical practice. Other approaches, such as should be directed towards the development of prophy- therapeutic vaccines that aim at stimulating the immune lactic, rather than therapeutic, cancer vaccines [2]. Pro- response of the host against tumor cells, were much less phylactic vaccines against viruses that increase the risk of successful [1]. Experimental evidence clearly shows that cancer, such as hepatitis B virus (HBV) or papilloma virus vaccines elicit effective responses against early, micro- (HPV), have already shown a significant effcacy in Page 1 of 18 (page number not for citation purposes) Immunome Research 2005, 1:5 http://www.immunome-research.com/content/1/1/5 reducing cancer incidence [3,4]. The challenge is now to target antigen. p185neu was combined with the two non devise immunological strategies for the design of prophy- specific adjuvants, allogeneic class I major histocompati- lactic vaccines for prevention of those human cancers that bility complex (MHCI) glycoproteins and interleukin 12 are not related to viral infections. (IL-12). MHCI glycoproteins are responsible for some of the most intense immune responses observed during the Standard vaccines against viruses induce the primary rejection of allogeneic organ transplants. Unlike conven- response of the adaptive components of the immune sys- tional antigens, allogeneic MHCI molecules stimulate a tem against the non-self antigen in order to activate the relatively large fraction of all T cell clones, up to 10% of immune system memory which will then elicit the much the available repertoire. IL-12 is a cytokine normally pro- stronger secondary response when the antigen will enter duced by antigen presenting cells (APC) such as dendritic the body. There is no need to break self tolerance as the cells (DC) to stimulate T helper cells and other cells of the antigen is non self. immune system, such as natural killer cells (NK) [7]. IL-12 was initially administered systemically, but a more recent At variance tumor vaccines need to break tolerance of the formulation of the Triplex vaccine used genetically modi- tumor associated antigens (TAA) that otherwise would be fied vaccine cells transduced with IL-12 genes, thus allow- treated as self and not attacked by the immune system. ing cytokine production at locally high levels that more closely mimicked the natural release of IL-12 [8]. The vac- The effectiveness of tumor immuno-prevention was dem- cine cell (VC) that we will model here is similar to the lat- onstrated in the past ten years in several mouse models of ter one and consists of a HER-2/neu transgenic mammary tumor development. Tumors in these models are induced carcinoma cell allogeneic with respect to the host and either by chemical carcinogens or by transgenic expres- transduced with IL-12 genes. sion of oncogenes. Among the most thoroughly investi- gated is the HER-2/neu transgenic mouse model. HER-2/ A complete prevention of mammary carcinogenesis with neu is an oncogene involved in human breast and ovary the Triplex vaccine was obtained when vaccination cycles carcinomas. The protein product of HER-2/neu, p185neu, started at 6 weeks of age and continued for the entire dura- is a membrane tyrosine kinase that transduces prolifera- tion of the experiment, at least one year (chronic vaccina- tive signals. A deregulation of HER-2/neu, for example tion). One vaccination cycle consisted of four due to gene amplification, leads to uncontrolled cell pro- intraperitoneal administrations of non-replicating (mito- liferation. Over-expression of a rat HER-2/neu transgene mycin-treated) VC over two weeks followed by two weeks in mice was obtained using tissue-specific regulatory of rest [8]. We made various attempts at reducing the sequences derived from mammary tumor virus (MMTV) number of vaccination cycles, in particular we studied the long terminal repeats (LTR). Various transgenic mouse effects of just three cycles starting at 6 weeks of age (early lines were obtained using either a mutant, constitutively vaccination), or at 10 weeks of age (late vaccination), or at activated HER-2/neu gene or a normal, non mutated gene. 16 weeks of age (very late vaccination). Early vaccination Here we will refer to mice carrying the mutant oncogene, produced a significant delay in the onset of tumors, but all which are prone to a very aggressive mammary carcino- mice eventually succumbed to mammary carcinoma. Late genesis, invariably leading to the development of invasive vaccination was less effective than early vaccination, mammary carcinomas by the age of 6 months. The natural whereas the very late protocol was completely devoid of history of mammary carcinoma in HER-2/neu transgenic effect in comparison to untreated control mice (Figure 1). mice was thoroughly investigated and found to be remarkably similar to that of human breast cancer [5]. The question whether the Chronic protocol is the mini- Immuno-prevention of mammary carcinoma in HER-2/ mal vaccination protocol yielding complete protection neu transgenic mice was attempted using various immu- from tumor onset, or whether a lower number of vaccina- nological strategies, including cytokines, non-specific tion cycles would provide a similar degree of protection is stimulators of the immune response, and HER-2/neu spe- still an open question. Finding an answer to this question cific vaccines made of DNA, proteins, peptides, or whole via a biological solution would be too expensive in time cells. Most approaches achieved a delay of mammary car- and money as it would require an enormous number of cinogenesis, but a complete prevention of tumor onset experiments, each lasting at least one year. For this reason was not attained, particularly in the most aggressive we developed an accurate model of immune system tumor models [6]. We achieved the first complete success responses to vaccination and we use this model as a virtual at preventing mammary carcinoma in HER-2/neu trans- laboratory to search for effective vaccination protocols. The genic mice using a vaccine that combined three different paper is organized as follows: section §2 will introduce stimuli for the immune system. The first was p185neu, the general requirements needed to model the problem; protein product of HER-2/neu, which in this system is at section §3 describes in details our virtual laboratory, i.e. the same time the oncogene driving carcinogenesis and the model, its structure and biological details, and its Page 2 of 18 (page number not for citation purposes) Immunome Research 2005, 1:5 http://www.immunome-research.com/content/1/1/5 task in an extremely effective and effcient way. Complex- ity, in this framework, is driven by the fact that interac- tions are developed at different scales (i.e. the cellular dynamics is ruled by sub-cellular interactions) and differ- ent mechanisms operate on the same subject (mechanical for the dynamics and biological for the immune competi- tion). The state of the art of the immune mechanisms from the view point of molecular biology are described in specialized literature [9-11]. Owing to the rapid progress of biological knowledge this is rapidly changing.
Load more

Recommended publications
  • Phylogenetic Analysis of the Human Antibody Repertoire Reveals Quantitative Signatures of Immune Senescence and Aging
    Phylogenetic analysis of the human antibody repertoire reveals quantitative signatures of immune senescence and aging Charles F. A. de Bourcya, Cesar J. Lopez Angelb, Christopher Vollmersc,1, Cornelia L. Dekkerd, Mark M. Davisb,e,f, and Stephen R. Quakea,c,g,2 aDepartment of Applied Physics, Stanford University, Stanford, CA 94305; bDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305; cDepartment of Bioengineering, Stanford University, Stanford, CA 94305; dDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305; eInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305; fHoward Hughes Medical Institute, Chevy Chase, MD 20815; and gChan Zuckerberg Biohub, San Francisco, CA 94158 Contributed by Stephen R. Quake, December 15, 2016 (sent for review November 4, 2016; reviewed by Nir Hacohen and Rob Knight) The elderly have reduced humoral immunity, as manifested by hypervariable complementarity-determining region 3 (CDR3) in increased susceptibility to infections and impaired vaccine re- Ig heavy-chain (IGH) transcripts (8, 9). sponses. To investigate the effects of aging on B-cell receptor Elderly individuals’ B-cell repertoires have been reported to (BCR) repertoire evolution during an immunological challenge, we exhibit restricted clonal diversity, oligoclonal character, increased used a phylogenetic distance metric to analyze Ig heavy-chain baseline mutation levels, and persistent clonal expansions in pre- transcript sequences in both young and elderly individuals before vious studies of IGH sequence diversity (8, 10). However, previous and after influenza vaccination. We determined that BCR reper- work was limited by small numbers of elderly individuals analyzed toires become increasingly specialized over a span of decades, but (8), did not analyze in detail the composition of the oligoclonal less plastic.
    [Show full text]
  • Head and Neck Cancer Immunoprevention J
    Published OnlineFirst November 14, 2017; DOI: 10.1158/1940-6207.CAPR-17-0331 Editorial Cancer Prevention Research The Next Frontier: Head and Neck Cancer Immunoprevention J. Silvio Gutkind1 and Jack D. Bui2 Abstract Restoring T cell–mediated antitumor immunity by targeting elicit an increased therapeutic response. New experimental studies immune checkpoint inhibitors in head and neck squamous cell suggest that immune therapies can be used for HNSCC prevention carcinoma (HNSCC) results in immunomodulation and durable rather than therapy. Given the current excitement for precision remissions. However, the overall response rate to these immu- medicine, these findings support the future development of notherapies in HNSCC is only approximately 20%. This raises the multimodality approaches for preventive immune oncology. possibility that immunologic intervention earlier in the HNSCC Cancer Prev Res; 10(12); 681–3. Ó2017 AACR. continuum, such as in oral premalignant lesions (OPL) could See related article by Jin Wang, et al., p. 684 Oral Premalignancy and Chemoprevention recognition and an antitumor immune response, including the recruitment of myeloid-derived suppressor cells and conditioning Every year, more than 600,000 cases of head and neck squa- of the surrounding microenvironment to become highly immu- mous cell carcinomas (HNSCC) are diagnosed worldwide. Pre- nosuppressive by expressing cytokines, such as IL6, IL10, and invasive tissue histologic abnormalities, such as dysplasia, often TGFb, leading to the accumulation of suppressive regulatory T represent early to intermediate stages of the carcinogenic process cells and the polarization of macrophages toward an immuno- during HNSCC progression. At a macroscopic level, these pre- suppressive (M2) tumor-associated macrophage phenotype (2).
    [Show full text]
  • Vaccines and Other Immunological Approaches for Cancer Immunoprevention
    Current Drug Targets, 2011, 12, 1957-1973 1957 Vaccines and Other Immunological Approaches for Cancer Immunoprevention Pier-Luigi Lollini*,1, Giordano Nicoletti2, Lorena Landuzzi2, Federica Cavallo3, Guido Forni3, Carla De Giovanni4 and Patrizia Nanni4 1Department of Hematology and Oncological Sciences, University of Bologna; 2Rizzoli Orthopedic Institute, Bologna; 3Molecular Biotechnology Center, Department of Clinical and Biological Sciences, University of Turin; 4Department of Experimental Pathology, University of Bologna, Italy Abstract: The immune system effectively prevents cancer, whereas severe immunodepression increases its incidence. Cancer immunoprevention is a strategy based on the concept that enhancement of tumor immunity in healthy individuals reduces cancer risk. It can be viewed as a kind of chemoprevention. For cancer immunoprevention, the cancer universe can be neatly divided between tumors caused - directly or indirectly - by infectious agents and all other tumors. Immunoprevention of tumors caused by infectious agents is already implemented at the population level for hepatitis B virus (HBV)-related hepatocellular carcinoma and for tumors caused by human papillomaviruses (HPV), like cervical carcinoma. Now the challenge is to develop immunological strategies to prevent the bulk (>80%) of human tumor burden, unrelated to infections. Both vaccines against tumor antigens and immune modulators can prevent tumor onset in cancer- prone mice. These studies outlined the target antigens and the molecular and cellular mechanisms
    [Show full text]
  • Chemoprevention of Preclinical Breast and Lung Cancer with the Bromodomain Inhibitor I-BET 762 Di Zhang1, Ana S
    Published OnlineFirst December 15, 2017; DOI: 10.1158/1940-6207.CAPR-17-0264 Research Article Cancer Prevention Research Chemoprevention of Preclinical Breast and Lung Cancer with the Bromodomain Inhibitor I-BET 762 Di Zhang1, Ana S. Leal1, Sarah Carapellucci1, Kayla Zydeck1, Michael B. Sporn2, and Karen T. Liby1 Abstract Breast cancer and lung cancer remain the top two However, few studies have investigated the chemo- leading causes of cancer-related deaths in women. preventive effects of bromodomain inhibitors. Here, Because of limited success in reducing the high mortality we found that I-BET 762 significantly delayed tumor of these diseases, new drugs and approaches are desper- development in preclinical breast and lung cancer ately needed. Cancer prevention is one such promising mouse models. This drug not only induced growth arrest strategy that is effective in both preclinical and clinical and downregulated c-Myc, pSTAT3, and pERK protein studies. I-BET 762 is a new bromodomain inhibitor that expression in tumor cells in vitro and in vivo but also reversibly targets BET (bromodomain and extraterminal) altered immune populations in different organs. These proteins and impairs their ability to bind to acetylated results demonstrate the promising potential of using lysines on histones, thus interrupting downstream I-BET 762 for cancer prevention and suggest the striking transcription. This inhibitor has anti-inflammatory effects of I-BET 762 are the result of targeting both effects and induces growth arrest in many cancers and tumor cells and the tumor microenvironment. Cancer is currently under clinical trials for treatment of cancer. Prev Res; 11(3); 143–56.
    [Show full text]
  • Efficiency of the Immunome Protein Interaction Network Increases During Evolution Csaba Ortutay*1 and Mauno Vihinen1,2
    Immunome Research BioMed Central Research Open Access Efficiency of the immunome protein interaction network increases during evolution Csaba Ortutay*1 and Mauno Vihinen1,2 Address: 1Institute of Medical Technology, FI-33014 University of Tampere, Finland and 2Tampere University Hospital, FI-33520 Tampere, Finland Email: Csaba Ortutay* - [email protected]; Mauno Vihinen - [email protected] * Corresponding author Published: 22 April 2008 Received: 23 January 2008 Accepted: 22 April 2008 Immunome Research 2008, 4:4 doi:10.1186/1745-7580-4-4 This article is available from: http://www.immunome-research.com/content/4/1/4 © 2008 Ortutay and Vihinen; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Details of the mechanisms and selection pressures that shape the emergence and development of complex biological systems, such as the human immune system, are poorly understood. A recent definition of a reference set of proteins essential for the human immunome, combined with information about protein interaction networks for these proteins, facilitates evolutionary study of this biological machinery. Results: Here, we present a detailed study of the development of the immunome protein interaction network during eight evolutionary steps from Bilateria ancestors to human. New nodes show preferential attachment to high degree proteins. The efficiency of the immunome protein interaction network increases during the evolutionary steps, whereas the vulnerability of the network decreases. Conclusion: Our results shed light on selective forces acting on the emergence of biological networks.
    [Show full text]
  • Harnessing the Immune System to Prevent Cancer: Basic Immunologic Mechanisms & Their Application to Clinical Trials of Vaccines Part 2: the Vaccines Barbara K
    Harnessing the Immune System to Prevent Cancer: Basic Immunologic Mechanisms & Their Application to Clinical Trials of Vaccines Part 2: The Vaccines Barbara K. Dunn NCI/Division of Cancer Prevention August 3, 2020 Harnessing the Immune System to Prevent Cancer: Basic Immunologic Mechanisms and Therapeutic Approaches that are Relevant to Cancer Prevention I. Basic immunologic mechanisms II. Application to prevention & treatment of cancer 1. Antibodies: as drugs 2. Vaccines: general principles & your vaccine trials & more… I) Vaccines to prevent cancers caused by infectious agents II) Vaccines to prevent non-infection associated cancer (directed toward tumor associated antigens) Harnessing the Immune System to Prevent Cancer: Basic Immunologic Mechanisms and Therapeutic Approaches that are Relevant to Cancer Prevention I. Basic immunologic mechanisms II. Application to prevention & treatment of cancer 1. Antibodies: as drugs “passive immunity” 2. Vaccines: general principles & your vaccine trials & more… I) Vaccines to prevent cancers caused by infectious agents “active II) Vaccines to prevent immunity” non-infection associated cancer (directed toward tumor associated antigens) Harnessing the Immune System to Prevent Cancer: Basic Immunologic Mechanisms and Therapeutic Approaches that are Relevant to Cancer Prevention I. Basic immunologic mechanisms II. Application to prevention & treatment of cancer 1. Antibodies:Focus as on drugs the Antigen “passive !immunity” 2. Vaccines: general principles & your vaccine trials & more… I) Vaccines
    [Show full text]
  • Cancer Moonshot: the Immuno-Oncology Translation
    Blue Ribbon Panel Recommendations A. Establish a network for direct patient involvement B. Create a translational science network devoted to immunotherapy C. Develop ways to overcome resistance to therapy D. Build a national cancer data ecosystem E. Intensify research on the major drivers of childhood cancer F. Minimize cancer treatment’s debilitating side effects G. Expand use of proven prevention and early detection strategies H. Mine past patient data to predict future patient outcomes I. Develop a 3D cancer atlas J. Develop new cancer technologies 13 Immuno-ImmunoOncology-Oncology Translational Translational Network Network (IOTN) Blue Ribbon Panel Immunotherapy and Prevention Accelerate translation of basic discoveries to clinical applications to improve immunotherapy outcomes for both “hot” and “cold” cancers - and to prevent cancers before they occur. Recommendation: Create a translational science network devoted to immunotherapy Implementation Plan: Build a collaborative network focused on: o Discovering and evaluating novel immune-based approaches to increase the number of patients that benefit from immunotherapy; and o Developing and validating early intervention vaccines to prevent cancers of all types o Incorporating multi-disciplinary approaches to improve immunotherapy 5 Cancer Immunotherapy Research Projects (U01) Objectives: Cancer Immunotherapy Sub-Networks o Define immune interactions in tumor microenvironments. Pancreatic o Identify novel immune checkpoints, tumor-specific T cell Other Lung receptors and their cognate tumor targets (neoantigens). Cancers Steering Committee Ovarian o Uncover intrinsic and extrinsic resistance pathways. Prostate Breast o Test improved immunotherapies, (vaccines, checkpoint Colorectal inhibitors, cellular or viral therapies, bispecific antibodies) o Studies should be largely pre-clinical involving clinically- relevant models and endpoints for rapid translation.
    [Show full text]
  • Immunome-Derived Epitope-Driven Vaccines (ID-EDV)
    Available online at www.sciencedirect.com Procedia in Vaccinology 1 (2009) 15–22 2nd Vaccine Global Congress, Boston 2008 Immunome-derived Epitope-driven Vaccines (ID-EDV) Protect against Viral or Bacterial Challenge in Humanized Mice Lenny Moisea,b, Matt Arditoa, Joe Desrosiersa, Jill Schriewerc, Mark Bullerd, Sharon E. Freyd, Stephen H. Gregoryb,e, Steven F. Mossb,d, Jinhee Leee, Hardy Kornfeld e, Bill Martina, Anne S. De Groota,b,c,* * aEpiVax, 146 Clifford Street, Providence, RI 02903, USA bAlpert Medical School, Brown University, Providence, RI 02903, USA cInstitute for Immunology and Informatics, University of Rhode Island, 80 Washington Street, Providence, RI 02903, USA d Saint Louis University, St. Louis, MO 63104, USA eLifespan, Rhode Island Hospital, Providence RI, 02903, USA fUniversity of Massachusetts Medical Center, Worcester, MA 01655, USA Abstract While whole killed, whole protein, or live attenuated vaccines were the standard bearers for protective vaccines in the last century, there are concerns about their safety. New vaccine design techniques are contributing to an emphasis on vaccines developed using the minimum essential subset of T- and B-cell epitopes that comprise the “immunome.” We have used bioinformatics sequence analysis tools, epitope-mapping tools, microarrays and high- throughput immunology assays to identify the minimal essential vaccine components for smallpox, tularemia, Helicobacter pylori and tuberculosis vaccines. As will be described in this review, this approach has resulted in the development of four immunome-derived epitope-driven vaccines (ID-EDV); three of these proved protective against viral or bacterial challenge. Protective efficacies of 100% (vaccinia), 90% (H. pylori), and 57% (tularemia) were achieved in HLA-transgenic (humanized) mouse models and the p27 knockout mouse (for H.
    [Show full text]
  • Citrullinated Protein Antibodies in Rheumatoid Arthritis
    ARTHRITIS & RHEUMATOLOGY Vol. 70, No. 12, December 2018, pp 1946–1958 DOI 10.1002/art.40587 © 2018, American College of Rheumatology Affinity Maturation Drives Epitope Spreading and Generation of Proinflammatory Anti–Citrullinated Protein Antibodies in Rheumatoid Arthritis Serra E. Elliott, Sarah Kongpachith, Nithya Lingampalli, Julia Z. Adamska, Bryan J. Cannon, Rong Mao, Lisa K. Blum, and William H. Robinson Objective. Rheumatoid arthritis (RA) is character- were observed (P < 0.01). Shared complementarity-deter- ized by the presence of anti–citrullinated protein antibod- mining region 3 sequence motifs were identified across ies (ACPAs); nevertheless, the origin, specificity, and subjects. A subset of the plasmablast lineages included functional properties of ACPAs remain poorly under- members derived from later time points with divergent stood. The aim of this study was to characterize the evolu- somatic hypermutations that encoded antibodies that tion of ACPAs by sequencing the plasmablast antibody bind an expanded set of citrullinated antigens. Further- repertoire at serial time points in patients with estab- more, these recombinant, differentially mutated plas- lished RA. mablast antibodies formed immune complexes that Methods. Blood samples were obtained at up to 4 stimulated higher macrophage production of tumor serial time points from 8 individuals with established RA necrosis factor (TNF) compared to antibodies represent- who were positive for ACPAs by the anti–cyclic citrulli- ing earlier time point–derived lineage members that were nated peptide test. CD19+CD3ÀIgDÀCD14ÀCD20À less mutated. CD27+CD38++ plasmablasts were isolated by single-cell Conclusion. These findings demonstrate that sorting and costained with citrullinated peptide established RA is characterized by a persistent IgA tetramers to identify ACPA-expressing plasmablasts.
    [Show full text]
  • Integration of Immunome with Disease Gene Network Reveals Pleiotropy and Novel Drug 2 Repurposing Targets
    bioRxiv preprint doi: https://doi.org/10.1101/2019.12.12.874321; this version posted December 13, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Integration of immunome with disease gene network reveals pleiotropy and novel drug 2 repurposing targets 3 Abhinandan Devaprasad1, Timothy RDJ Radstake1, Aridaman Pandit1* 4 1 Center for Translation Immunology, University Medical Center Utrecht, Utrecht, The 5 Netherlands 6 *Correspondence: Aridaman Pandit: [email protected] 7 8 Abstract 9 Immune system is crucial for the development and progression of immune-mediated and non- 10 immune mediated complex diseases. Studies have shown that multiple complex diseases are 11 associated with several immunologically relevant genes. Despite such growing evidence, the 12 effect of disease associated genes on immune functions has not been well explored. Here, we 13 curated the largest immunome (transcriptome profiles of 40 different immune cells) and 14 integrated it with disease gene networks and drug-gene database, to generate a Disease-gene 15 IMmune cell Expression network (DIME). We used the DIME network to: (1) study 13,510 16 genes and identify disease associated genes and immune cells for >15,000 complex diseases; 17 (2) study pleiotropy between various phenotypically distinct rheumatic and other non- 18 rheumatic diseases; and (3) identify novel targets for drug repurposing and discovery. We 19 implemented DIME as a tool (https://bitbucket.org/systemsimmunology/dime) that allows 20 users to explore disease-immune-cell associations and disease drug networks to pave way for 21 future (pre-) clinical research.
    [Show full text]
  • Immunome Discovery Engine Simultaneously Identifies Antibodies and Their Antigen Targets by Interrogating the Patient’S Memory B Cells in an Unbiased Manner
    Developing Antibody‐Based Therapeutics by Unlocking the Human Memory B Cell Response Immunome, Inc. 665 Stockton Drive, Suite 300 Exton, PA 19341 October 26, 2020 610.321.3700 www.immunome.com Forward Looking Statements This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. The Company intends forward-looking terminology such as “believes,” “anticipates,” “plans,” “may,” “intends,” “will,” “should,” “expects,” and similar expressions to identify forward-looking statements. Further, forward-looking statements include, but are not limited to, statements regarding the Company’s financial position, strategy, business plans, expectations regarding the timing and achievement of its product candidate development activities and ongoing and planned preclinical studies and clinical trials, plans and expectations for future operations and research and development initiatives. Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking statements. These forward-looking statements involve risks and uncertainties, including regarding the Company’s expectation that it will incur net losses for the foreseeable future, and that it may never be profitable; its need for additional funding; the timing and success of preclinical studies and clinical trials it conducts; the ability to obtain and maintain regulatory approval of its product candidates; the ability to commercialize its product candidates; its ability to compete in the marketplace; developments relating to the COVID-19 pandemic; its ability to obtain and maintain intellectual property protection for its product candidates; and its ability to manage growth. These or other risks or uncertainties may cause the Company’s actual results to differ materially from any forward-looking statements.
    [Show full text]
  • An Integrated Genomic and Immunoinformatic Approach to H
    University of Rhode Island DigitalCommons@URI Institute for Immunology and Informatics Faculty Institute for Immunology and Informatics (iCubed) Publications 2011 An Integrated Genomic and Immunoinformatic Approach to H. pylori Vaccine Design Matthew Ardito Joanna Fueyo See next page for additional authors Creative Commons License This work is licensed under a Creative Commons Attribution 3.0 License. Follow this and additional works at: https://digitalcommons.uri.edu/immunology_facpubs Terms of Use All rights reserved under copyright. Citation/Publisher Attribution Ardito, M., Fueyo, J., Tassone, R., Terry, F., DaSilva, K., Zhang, S., Martin, W., De Groot, A. S., Moss, S. F., & Moise, L. (2011). An Integrated Genomic and Immunoinformatic Approach to H. pylori Vaccine Design. Immunome Research, 7(2). Available at: http://dx.doi.org/10.4172/1745-7580.1000049 This Article is brought to you for free and open access by the Institute for Immunology and Informatics (iCubed) at DigitalCommons@URI. It has been accepted for inclusion in Institute for Immunology and Informatics Faculty Publications by an authorized administrator of DigitalCommons@URI. For more information, please contact [email protected]. Authors Matthew Ardito, Joanna Fueyo, Ryan Tassone, Frances Terry, Kristin DaSilva, Songhua Zhang, William Martin, Anne S. De Groot, Steven F. Moss, and Leonard Moise This article is available at DigitalCommons@URI: https://digitalcommons.uri.edu/immunology_facpubs/32 Ardito et al. Immunome Research 2011, 7:2:1 http://www.immunome-research.net/ RESEARCH Open Access An Integrated Genomic and Immunoinformatic Approach to H. pylori Vaccine Design Matthew Ardito1, Joanna Fueyo2¶, Ryan Tassone1, Frances Terry1, Kristen DaSilva3, Songhua Zhang4, Wil- liam Martin1, Anne S.
    [Show full text]