DOCSLIB.ORG

Adjuvanted Corn Nanoparticle Enhances the Breadth of Inactivated

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Adjuvanted Corn Nanoparticle Enhances the Breadth of Inactivated Poly(I:C) adjuvanted corn nanoparticle enhances the breadth of inactivated influenza virus vaccine immune response in pigs Thesis Presented in Partial Fulfillment of the Requirements for the Degree Master of Science in the Graduate School of The Ohio State University By Ninoshkaly Feliciano Ruiz, B.S. BiomedSc Graduate Program in Comparative and Veterinary Medicine The Ohio State University 2020 Thesis Committee Dr. Renukaradhya J. Gourapura, Advisor Dr. Feng Qu Dr. Scott P. Kenney 1 Copyrighted by Ninoshkaly Feliciano Ruiz 2020 2 Abstract Influenza A virus (IAV) is known for causing respiratory viral infections in a broad spectrum of birds and mammals, including humans and pigs. Pig acts as a mixing vessel for the generation of new reassortant IAV viruses of pandemic potential, like the 2009 H1N1 virus strain. The most common method to control of IAV in farms is by the intramuscular (IM) immunization of pig with killed multivalent IAV vaccine. However, IM immunization induces poor mucosal secretory IgA (SIgA) antibody response in the airways and thus confers highly variable levels of protection. Intranasal (IN) immunization studies using nanoparticle-based IAV vaccines in pigs have shown to increase the specific mucosal SIgA antibody response, cell-mediated immune response and enhances the production of pro-inflammatory cytokines. In this study, we overview the pig immune system to fight IAV infections, different vaccination strategies and several adjuvants that have been tested in pig against swine influenza. Recently, we develop and characterized a sweet corn-derived cationic alpha-D-glucan nanoparticle (Nano-11) and established its adjuvant potential in mice and pigs. With the objective of improving cross-reactivity of the Nano-11 based killed IAV antigens (Nano-11-KAg) vaccine induced immune responses, in this study, we assessed the combinatorial effect Nano-11 adsorbed with both KAg and a secondary adjuvant poly(I:C) Nano-11-KAg- poly(I:C) in induction of the mucosal and systemic immune responses and efficacy ii against a heterologous IAV challenge infection in pigs. Our data showed that Nano-11- KAg-poly(I:C) vaccine elicited cross-reactive SIgA production in the nasal passage and lungs and IgG antibody in the lungs against vaccine virus (H1N2-OH10), challenge virus (H1N1-OH7), and a heterosubtypic H3N2-OH4 SwIAV. In addition, Nano-11-KAg- poly(I:C) vaccine augmented mRNA expression of the cytokines IL-2, IL-6, IL-10, IL- 13, and TNF-α, and the transcription factor GATA3 in tracheobronchial lymph nodes compared to a commercial multivalent SwIAV vaccine. Also, Nano-11-KAg-poly(I:C) elicited high levels of virus neutralizing antibodies in bronchoalveolar lavage fluid and the frequency of IFNγ secreting γδ T cells. However, reduction in microscopic lung lesions and heterologous challenge virus load in both the Nano-11-KAg and commercial vaccine received animals was partial. In summary, compared to our earlier study using Nano-11-KAg vaccine, addition of poly(I:C) improved the cross-reactive antibody and cytokine responses in intranasal immunized pigs. Future studies will be aimed at improving the breadth of immunity of Nano-11-KAg vaccine using KAg of multivalent SwIA strains in pigs. iii Acknowledgments First of all, I want to thank my advisor Dr. Gourapura for his support and guidance during the past two years. I met Dr. Gourapura two years before starting my master's degree as an undergrad student through the Summer Research Opportunity Program (SROP) during summer 2016 and 2017. Many things happened in my life before starting the program at OSU that led me to wonder if I could come and study in the United States. In my last semester of bachelor (2017), the University of Puerto Rico participated in a national strike for four months, causing a delay in the graduation date. Then on September 20, 2017, Puerto Rico was hit by a category 5 hurricane, called María an atmospheric event that changed our lives forever. During the emergency, I wondered if it was still possible to finish my OSU application on time because in PR everything was paralyzed, we had neither electricity, water nor internet, my hopes of taking the GRE exam and finishing my undergrad coursework on time were fading. As soon as I got a signal on my cell phone, I wrote an email to Dr. Gourapura to let him know the situation. I also called Pamela Thomas (SROP manager) to let her know that I was still interested in grad school and if she could help me in the process. Thanks to the help of Dr. Gourapura and Pamela, today, I am closer to achieving my goal to complete my master's degree in the Comparative and Veterinary Medicine Program. iv I will always be grateful to Dr. Santosh Dhakal, a Ph.D. student in Dr. Gourapura’s Lab. Santosh played a crucial role in my training as a student. He taught me how to correctly use a pipette all the way until how to draw blood from pigs and extract the immune cells. I also want to thank Shristi Ghimire (past lab technician in our lab) for her help in the laboratory and for being that key person that took my hand when my world crashed to the floor when I almost lost my father due to a heart attack. I thank my coworkers Dr. Sankar Renu, Ph.D. student Yi Han and Jennifer Schrock, for their help during animal trials, for making the lab more enjoyable and for light moments when the experiments did not work, and results were not as expected. My appreciation also goes to the animal care staff Dr. Juliette Hanson, Sara Talmadge, Megan Strother, and the department secretary staffs Hannah Gehman and Robin Weimer. Food Animal Health Research Program (FAHRP) is a small department with few students where we share similar experiences in the labs. That is why I want to thank the graduate students KC, Kush, Abundo, and Gary for sharing their advice regarding academic writing, to help me find housing in Columbus, suggestions for my master's coursework, and for cheers and unplanned group therapies during our graduate studies. Wooster has given me beautiful experiences and friendship that will last forever. Outside the scope of the laboratory, I want to thank my friends Edna and Adriana Alfaro for being like my sisters and making me feel at home. I also include Camila, Lourdes, Seyed Hashem, Yosmer, and Erick for planning the adventures and parties that cheered our weekends. I also recognized the efforts of my family, especially my parents and my grandparents, who came to visit me or bought me the flight ticket for a weekend so I v could spend time with them. Thanks to all who in one way or another have helped me during this time, and I hope to continue with my studies always with God ahead. vi Vita 2013-2017……...................B.S., Biomedicine, University of Puerto Rico at Ponce May 2018 to present ..........M.S. Comparative and Veterinary Medicine (CVM), The Ohio State University Publications 1. Renu S*, Feliciano-Ruiz N*, Ghimire S, Han Y, Schrock J, Dhakal S, Patil V, Krakowka S, Renukaradhya G.J. (2020). Poly(I:C) adjuvanted corn nanoparticle enhances the breadth of inactivated influenza virus vaccine immune response in pigs. Manuscript submitted to Frontiers in immunology. *contributed equally 2. Renu S, Feliciano-Ruiz N, Ghimire S, Han Y, Schrock J, Dhakal S, Patil V, Krakowka S, Renukaradhya G.J. (2020). Poly(I:C) augments inactivated influenza virus-chitosan nanovaccine induced cell mediated immune response in pigs vaccinated intranasally, Veterinary Microbiology, doi: https://doi.org/10.1016/j.vetmic.2020.108611 3. S. Dhakal, S. Renu, S. Ghimire, Y.S. Lakshmanappa, B.T. Hogshead, N. Feliciano-Ruiz, F. Lu, H. HogenEsch, S. Krakowka, C.W. Lee, G.J. Renukaradhya. (2018). Mucosal Immunity and Protective Efficacy of Intranasal vii Inactivated Influenza Vaccine is Improved by Chitosan Nanoparticle Delivery in Pigs. Frontiers in Immunology; 2018; 9: 934. 4. Dhakal, S., Cheng, X., Salcido, J., Renu, S., Bondra, K., Lakshmanappa, Y. S., Misch, C., Ghimire, S., Feliciano-Ruiz, N., Hogshead, B., Krakowka, S., Carson, K., McDonough, J., Lee, C. W. and Renukaradhya, G. J. (2018). Liposomal nanoparticle-based conserved peptide influenza vaccine and monosodium urate crystal adjuvant elicit protective immune response in pigs. Int J Nanomedicine, 13, 6699-6715. doi:10.2147/IJN.S178809. Fields of Study Major Field: Comparative and Veterinary Medicine Immunology and Vaccine Development viii Table of Contents Abstract .......................................................................................................................... ii Acknowledgments ......................................................................................................... iv Vita .............................................................................................................................. vii Table of Contents .......................................................................................................... ix List of Tables................................................................................................................xiv List of Figures ............................................................................................................... xv Chapter 1. Introduction ....................................................................................................1 1.1 Influenza A virus ...............................................................................................1 1.1.1 IAV nomenclature ..........................................................................................2 1.1.2 IAV structure
Load more

Recommended publications
  • Kate Fitzgerald
    In This Issue: 2020 Young Investigator Awardees pg. 3-9 In Memorium page pg. 14-15 New Member Mini-Bios pg. 19-21 Trials of Interferon Lambda pg. 31 Cytokines 2021 Hybrid Meetin pg. 24-27 Signals THE INTERNATIONAL CYTOKINE & INTERFERON SOCIETY + NEWSLETTER APRIL 2021 I VOLUME 9 I NO. 1 A NOTE FROM THE ICIS PRESIDENT Kate Fitzgerald Dear Colleagues, Greetings from the International Cytokine and Interferon Society! I hope you and your family are staying safe during these still challenging times. Thankfully 2020 is behind us now. We have lived through the COVID-19 pandemic, an event that will continue to impact our lives for some time and likely alter how we live in the future. Despite the obvious difficulties of this past year, I can’t help but marvel at the scientific advances that have been made. With everything from COVID-19 testing, to treatments and especially to the rapid pace of vaccine development, we are so better off today than even a few months back. The approval of remarkably effective COVID-19 vaccines now rolling out in the US, Israel, UK, Europe and across the globe, brings light at the end of the tunnel. The work of many of you has helped shape our understanding of the host response to Sars-CoV2 and the ability of this virus to limit antiviral immunity while simultaneously driving a cytokine driven hyperinflammatory response leading to deadly consequences for patients. The knowledge gained from all of your efforts has been put to good use to stem the threat of this deadly virus.
    [Show full text]
  • Hemispherx Biopharma, Inc
    Hemispherx Biopharma, Inc. HEB‐NYSE EXECUTIVE INFORMATIONAL OVERVIEW® November 27, 2016 Company Description Hemispherx Biopharma, Inc. (or “the Company”) is a specialty pharmaceutical company addressing critical unmet medical needs. The Company has invested over two decades of R&D into safe, effective ways to modulate and amplify the immune system, and is now poised to enter a confirmatory Phase III U.S. trial with an RNA† Hemispherx Biopharma, Inc. macromolecule that could become the only FDA‐approved therapy 1617 JFK Blvd., Suite 500 for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). Philadelphia, PA 19103 This candidate, Ampligen®, was approved for CFS/ME in Argentina in Phone: (215) 988‐0080 August 2016 and is available to patients in Europe through an early access program (EAP). CFS/ME is a debilitating disease with no Fax: (215) 988‐1739 www.hemispherx.net/ known treatment to date but very active patient advocacy groups. Hemispherx also holds rights to an FDA‐approved product for genital warts, Alferon N Injection®, which is believed to be the world’s only Ticker (Exchange) HEB (NYSE) approved natural interferon (IFN). Hemispherx has refined Alferon’s Recent Price (11/25/2016)* $0.85 manufacturing to drastically increase efficiencies and reduce costs, and now seeks FDA approval for the new production method before 52‐week Range $0.72 ‐ $2.64 relaunching Alferon. Hemispherx is headquartered in Philadelphia Shares Outstanding** ~24.1 million with GMP manufacturing and research facilities in New Jersey. Market Capitalization ~$20.5 million Average 3‐month Volume 110,574 Key Points Insider Ownership ~3.6 million The Ampligen® technology has also shown utility as a broad‐ Institutional Ownership ~5% spectrum antiviral that could help seasonal flu vaccines work EPS (Qtr.
    [Show full text]
  • COVID-19 Treatment and Vaccine Tracker This Document Contains an Aggregation of Publicly Available Information from Validated Sources
    COVID-19 Treatment and Vaccine Tracker This document contains an aggregation of publicly available information from validated sources. It is not an endorsement of one approach or treatment over another but simply a list of all treatments and vaccines currently in development. TREATMENTS Current Type of FDA-Approved Clinical Trials for Funding Clinical Trials for Anticipated Next Number Developer/Researcher Stage of Published Results Sources Product - Treatment Indications Other Diseases Sources COVID-19 Steps Timing Development ANTIBODIES PhRMA Begin Phase 1 trials in late Polyclonal hyperimmune Alliance among Takeda, CSL Behring, Wall Street Journal spring. To patients between 1 globulin (H-IG), formerly N/A Biotest AG, Bio Products Laboratory, Pre-clinical Pink Sheet December 2020 and December known at TAK-888 LFB, and Octapharma Press release from the 2021 alliance Biomedical Stat News Advanced MarketWatch Antibodies from mice, Research and Reuters 2 REGN3048-3051, against the N/A Regeneron Pre-clinical Start Phase 1 June 2020 Development Bloomberg News spike protein Authority FierceBiotech (BARDA) FiercePharma Korea Herald Antibodies from recovered 3 N/A Celltrion Pre-clinical Start Phase 1 in July 2020 UPI COVID-19 patients Celltrion press release Super-antibody or antibody 4 cocktail to target potential N/A Celltrion Pre-clinical Celltrion press release mutations of SARS-CoV-2 Antibodies from recovered BioSpace 5 N/A Kamada Pre-clinical COVID-19 patients AbbVie Stat News Antibodies from recovered 6 N/A Vir Biotech/WuXi Biologics/Biogen Pre-clinical Start Phase 1 ~ July 2020 Vir Biotech COVID-19 patients Vir Biotech * Indicates updated or new field This document contains an aggregation of publicly available information from validated sources.
    [Show full text]
  • Public Summary of Opinion on Orphan Designation Rintatolimod for the Treatment of Ebola Virus Disease
    19 May 2015 EMA/COMP/204227/2015 Committee for Orphan Medicinal Products Public summary of opinion on orphan designation Rintatolimod for the treatment of Ebola virus disease On 24 April 2015, orphan designation (EU/3/15/1480) was granted by the European Commission to NV Hemispherx BioPharma Europe, Belgium, for rintatolimod for the treatment of Ebola virus disease. What is Ebola virus disease? Ebola virus disease is a severe disease caused by infection with viruses known as ebolaviruses. There are 5 known species of ebolavirus, 4 of which are known to cause the disease in humans. Zaire ebolavirus, sometimes referred to simply as ‘ebola virus’ or EBOV, is the cause of the largest outbreaks of the disease to date and has led to the most deaths. Infection is caused by contact with the body fluids of an infected person. After infection there is an incubation period of between 2 to 21 days, following which the newly infected person starts to experience symptoms. The first symptoms typically are fever, headache, fatigue, muscle pain and sore throat. These are followed by other symptoms such as diarrhoea, vomiting, rash, kidney and liver problems and, in some cases, internal bleeding and bleeding from the gums, eyes, nose and ears. Patients are infectious once they start experiencing symptoms. Ebola virus disease is a life-threatening condition that is frequently fatal due to fluid loss and severe bleeding. What is the estimated number of patients affected by the condition? At the time of designation, Ebola virus disease affected less than 0.01 in 10,000 people in the European Union (EU).
    [Show full text]
  • Overview of Planned Or Ongoing Studies of Drugs for the Treatment of COVID-19
    Version of 16.06.2020 Overview of planned or ongoing studies of drugs for the treatment of COVID-19 Table of contents Antiviral drugs ............................................................................................................................................................. 4 Remdesivir ......................................................................................................................................................... 4 Lopinavir + Ritonavir (Kaletra) ........................................................................................................................... 7 Favipiravir (Avigan) .......................................................................................................................................... 14 Darunavir + cobicistat or ritonavir ................................................................................................................... 18 Umifenovir (Arbidol) ........................................................................................................................................ 19 Other antiviral drugs ........................................................................................................................................ 20 Antineoplastic and immunomodulating agents ....................................................................................................... 24 Convalescent Plasma ...........................................................................................................................................
    [Show full text]
  • Immune Responses Elicited by Live Attenuated Influenza Vaccines As
    Review Immune Responses Elicited by Live Attenuated Influenza Vaccines as Correlates of Universal Protection against Influenza Viruses Yo Han Jang 1,2 and Baik L. Seong 3,4,* 1 Department of Biological Sciences and Biotechnology Major in Bio-Vaccine Engineering, Andong National University, Andong 1375, Korea; [email protected] 2 Vaccine Industry Research Institute, Andong National University, Andong 1375, Korea 3 Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Korea 4 Vaccine Innovation Technology Alliance (VITAL)-Korea, Yonsei University, Seoul 03722, Korea * Correspondence: [email protected]; Tel.: +82-2-2123-7416 Abstract: Influenza virus infection remains a major public health challenge, causing significant mor- bidity and mortality by annual epidemics and intermittent pandemics. Although current seasonal influenza vaccines provide efficient protection, antigenic changes of the viruses often significantly compromise the protection efficacy of vaccines, rendering most populations vulnerable to the viral infection. Considerable efforts have been made to develop a universal influenza vaccine (UIV) able to confer long-lasting and broad protection. Recent studies have characterized multiple immune correlates required for providing broad protection against influenza viruses, including neutralizing antibodies, non-neutralizing antibodies, antibody effector functions, T cell responses, and mucosal immunity. To induce broadly protective immune responses by vaccination, various strategies using Citation: Jang, Y.H.; Seong, B.L. Immune Responses Elicited by Live live attenuated influenza vaccines (LAIVs) and novel vaccine platforms are under investigation. Attenuated Influenza Vaccines as Despite superior cross-protection ability, very little attention has been paid to LAIVs for the develop- Correlates of Universal Protection ment of UIV.
    [Show full text]
  • 2018 Medicines in Development for Cancer
    2018 Medicines in Development for Cancer Bladder Cancer Product Name Sponsor Indication Development Phase ABI-009 AADi Bioscience non-muscle invasive bladder cancer Phase I/II (nab-rapamycin/mTOR inhibitor) Los Angeles, CA www.aadibio.com ALT-801 Altor BioScience non-muscle invasive bladder cancer Phase I/II (tumor antigen-specific T-cell Miramar, FL www.altorbioscience.com receptor linked to IL-2) NantKwest Culver City, CA ALT-803 Altor BioScience non-muscle invasive bladder cancer Phase II (IL-15 superagonist protein complex) Miramar, FL (BCG naïve) (Fast Track), www.altorbioscience.com NantKwest non-muscle invasive bladder cancer Culver City, CA (BCG unresponsive) (Fast Track) B-701 BioClin Therapeutics 2L locally advanced or metastatic Phase I/II (anti-FGFR3 mAb) San Ramon, CA bladder cancer www.bioclintherapeutics.com Bavencio® EMD Serono 1L urothelial cancer Phase III avelumab Rockland, MA www.emdserono.com (anti-PD-L1 inhibitor) Pfizer www.pfizer.com New York, NY BC-819 BioCanCell Therapeutics non-muscle invasive bladder cancer Phase II (gene therapy) Cambridge, MA (Fast Track) www.biocancell.com Medicines in Development: Cancer ǀ 2018 1 Bladder Cancer Product Name Sponsor Indication Development Phase Capzola® Spectrum Pharmaceuticals non-muscle invasive bladder cancer application submitted apaziquone Henderson, NV (Fast Track) www.sppirx.com Cavatak® Viralytics bladder cancer (+pembrolizumab) Phase I coxsackievirus Sydney, Australia www.viralytics.com CG0070 Cold Genesys non-muscle invasive bladder cancer Phase II (oncolytic immunotherapy)
    [Show full text]
  • Local and Regional Therapy for Primary and Locally Recurrent Melanoma
    Local and Regional Therapy for Primary and Locally Recurrent Melanoma Justin G. Wilkes, MD,1,2 Ayushi Patel, BS,2 and Jonathan S. Zager, MD1,2 1Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida 2University of South Florida Morsani College of Medicine, Tampa, Florida Corresponding author: Abstract: In the vast majority of cases, cutaneous melanoma Jonathan S. Zager, MD pre sents as localized disease and is treated with wide excision and Moffitt Cancer Center sentinel lymph node biopsy, with shared decision making regard- 10920 North McKinley Drive ing completion lymph node dissection and adjuvant systemic Room 4.4123 Tampa, FL 33612 therapy. The treatment of recurrent and in-transit disease is more Tel: (813) 745-1085 complex, with further options for regional and systemic therapies Fax: (813) 745-5725 and multiple variables to be factored into decisions. Rates of over- Email: [email protected] all and complete response to regional therapies can be quite high in carefully chosen patients, which limits the need for systemic therapies and their inherent side effects. Ongoing trials aim to assess the efficacy of combination regional and systemic therapies and assist in deciding among these options. This review discusses the treatment of primary melanoma and regional nodal disease and offers an in-depth discussion of options for the treatment of recurrent melanoma and in-transit melanoma. Introduction Melanoma is the fifth most common cancer in the United States and the 17th-leading cause of cancer-related death, with recent declines in mortality following US Food and Drug Administration (FDA) approval of immunotherapy and targeted therapy agents.1 Newly diagnosed melanoma most commonly presents as primary disease, accounting for 84% of patients.
    [Show full text]
  • Roles of Type I and III Interferons in COVID-19
    Review Article Yonsei Med J 2021 May;62(5):381-390 https://doi.org/10.3349/ymj.2021.62.5.381 pISSN: 0513-5796 · eISSN: 1976-2437 Yongwoon Grand Prize in Medicine Roles of Type I and III Interferons in COVID-19 Hojun Choi1,2 and Eui-Cheol Shin2,3 1Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon; 2Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon; 3The Center for Epidemic Preparedness, KAIST Institute, Daejeon, Korea. Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I and III interferon (IFN) responses act as the first line of defense against viral infection and are activated by the recognition of viruses by infected cells and innate immune cells. Dysregulation of host IFN responses has been known to be associated with severe disease progression in COVID-19 patients. However, the reported results are controversial and the roles of IFN responses in COVID-19 need to be investigated further. In the absence of a highly efficacious antiviral drug, clinical studies have evaluated recombinant type I and III IFNs, as they have been successfully used for the treatment of infections caused by two other epidemic coronaviruses, SARS-CoV-1 and Middle East respiratory syndrome (MERS)-CoV. In this review, we describe the strategies by which SARS-CoV-2 evades IFN responses and the dysregulation of host IFN responses in COVID-19 patients. In ad- dition, we discuss the therapeutic potential of type I and III IFNs in COVID-19.
    [Show full text]
  • Minutes of the COMP Meeting 19-21 January 2021
    10 March 2021 EMA/COMP/64530/2021 Human Medicines Division Committee for Orphan Medicinal Products (COMP) Minutes for the meeting on 19-21 January 2021 Chair: Violeta Stoyanova-Beninska – Vice-Chair: Armando Magrelli 19 January 2021, 08:30-19:35, remote virtual meeting 20 January 2021, 08:30-19:50, remote virtual meeting 21 January 2021, 08:30-17:35, remote virtual meeting Disclaimers Some of the information contained in this set of minutes is considered commercially confidential or sensitive and therefore not disclosed. With regard to intended therapeutic indications or procedure scopes listed against products, it must be noted that these may not reflect the full wording proposed by applicants and may also vary during the course of the review. Additional details on some of these procedures will be published in the COMP meeting reports once the procedures are finalised. Of note, this set of minutes is a working document primarily designed for COMP members and the work the Committee undertakes. Further information with relevant explanatory notes can be found at the end of this document. Note on access to documents Some documents mentioned in the minutes cannot be released at present following a request for access to documents within the framework of Regulation (EC) No 1049/2001 as they are subject to on- going procedures for which a final decision has not yet been adopted. They will become public when adopted or considered public according to the principles stated in the Agency policy on access to documents (EMA/127362/2006). Official address Domenico Scarlattilaan 6 ● 1083 HS Amsterdam ● The Netherlands Address for visits and deliveries Refer to www.ema.europa.eu/how-to-find-us An agency of the European Send us a question Go to www.ema.europa.eu/contact Telephone +31 (0)88 781 6000 Union © European Medicines Agency, 2021.
    [Show full text]
  • Classification of Current Anticancer Immunotherapies
    www.impactjournals.com/oncotarget/ Oncotarget, Vol. 5, No. 24 Classification of current anticancer immunotherapies Lorenzo Galluzzi1,2,3,4,*, Erika Vacchelli1,2,3, José-Manuel Bravo-San Pedro1,2,3, Aitziber Buqué1,2,3, Laura Senovilla1,2,3, Elisa Elena Baracco1,2,3,5, Norma Bloy1,2,3,5, Francesca Castoldi1,2,3,5,6, Jean-Pierre Abastado7, Patrizia Agostinis8, Ron N. Apte9, Fernando Aranda1,2,3,10, Maha Ayyoub11,12, Philipp Beckhove13, Jean-Yves Blay14,15, Laura Bracci16, Anne Caignard17,18, Chiara Castelli19, Federica Cavallo20, Estaban Celis21, Vincenzo Cerundolo22, Aled Clayton23,24, Mario P. Colombo19, Lisa Coussens25, Madhav V. Dhodapkar26, Alexander M. Eggermont3, Douglas T. Fearon27, Wolf H. Fridman2,4,28,29, Jitka Fučíková6,30, Dmitry I. Gabrilovich31, Jérôme Galon2,4,28,32, Abhishek Garg8, François Ghiringhelli33,34,35, Giuseppe Giaccone36,37, Eli Gilboa38, Sacha Gnjatic39, Axel Hoos40, Anne Hosmalin4,41,42,43, Dirk Jäger44, Pawel Kalinski45,46,47, Klas Kärre48, Oliver Kepp1,2,49, Rolf Kiessling50, John M. Kirkwood51, Eva Klein48, Alexander Knuth52, Claire E. Lewis53, Roland Liblau54,55,56, Michael T. Lotze45,46, Enrico Lugli57, Jean-Pierre Mach58, Fabrizio Mattei16, Domenico Mavilio57,59, Ignacio Melero60,61, Cornelis J. Melief62,63, Elizabeth A. Mittendorf64, Lorenzo Moretta65, Adekunke Odunsi66, Hideho Okada67, Anna Karolina Palucka68, Marcus E. Peter69, Kenneth J. Pienta70, Angel Porgador9, George C. Prendergast71,72,73, Gabriel A. Rabinovich74, Nicholas P. Restifo75, Naiyer Rizvi76, Catherine Sautès- Fridman2,4,28,29, Hans Schreiber77, Barbara Seliger78, Hiroshi Shiku79, Bruno Silva- Santos80, Mark J. Smyth81,82, Daniel E. Speiser83,84, Radek Spisek6,30, Pramod K. Srivastava85,86, James E. Talmadge87, Eric Tartour4,88,89,90, Sjoerd H.
    [Show full text]
  • Diligence and Valuation Report
    Diligence and Valuation Report Arrowhead Code: 69-03-02 Company: Hemispherx Biopharma Inc. Coverage initiated: 06 November 2014 Ticker: NYSE MKT:HEB This document: 21 February 2015 Headquarters: Philadelphia, Pennsylvania Fair share value bracket – DCF $1.67 - $2.79 Chairman, CEO, President, CSO: Dr. William A. Carter, M.D. Share price 20 February 2015: $0.24i CFO: Mr. Thomas K. Equels, Esq. Analyst Team Senior VP of Operations Mr. Wayne S. Springate Snehal Mahajan Website: www.hemispherx.net +1 (212) 619-6889 [email protected] Market Data Innovative product pipeline; Alferon N Injection® - 52-Week Range: $0.21– $0.49ii Nearing Commercialization Average Daily Volume (3M Avg.): 1,487,786iii Arrowhead is updating coverage on Hemispherx Biopharma Market Cap (20 Feb. 2015) : $52.8 MM Inc. with a fair value bracket of $1.67 in the low bracket and $2.79 in the high bracket scenario using the Discounted Cash Financial Forecast (in USD) (FY Ending – Dec.) Flow (DCF) Valuation Method. '14E '15E '16E '17E '18E '19E '20E Key Highlights: (1) Alferon N Injection® presents a huge High NI (12.3) (4.4) 45.4 77.7 143.6 151.9 106.7 growth potential for the Company due to growing number of (MM) High patients in US suffering from genital warts, a common clinical (0.06) (0.02) 0.21 0.35 0.65 0.69 0.49 EPS manifestation of HPV infection;(2) Further, Alferon N Low NI ® (12.3) (4.4) 23.8 41.3 81.5 87.9 94.4 Injection is the only natural interferon approved by FDA for (MM) Low marketing in the US and hence the Company enjoys a (0.06) (0.02) 0.11 0.19 0.37 0.40 0.43 EPS favorable competitive position; (3) The Company is Company Overview: Based in Philadelphia, conducting work, based on published studies, on the potential Pennsylvania, Hemispherx Biopharma Inc.
    [Show full text]