DOCSLIB.ORG

Addressing Barriers to Effective Cancer Immunotherapy with Nanotechnology: Achievements, Challenges, and Roadmap to the Next Generation of Nanoimmunotherapeutics

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Addressing Barriers to Effective Cancer Immunotherapy with Nanotechnology: Achievements, Challenges, and Roadmap to the Next Generation of Nanoimmunotherapeutics Advanced Drug Delivery Reviews 141 (2019) 3–22 Contents lists available at ScienceDirect Advanced Drug Delivery Reviews journal homepage: www.elsevier.com/locate/addr Addressing barriers to effective cancer immunotherapy with nanotechnology: achievements, challenges, and roadmap to the next generation of nanoimmunotherapeutics Enping Hong, Marina A. Dobrovolskaia ⁎ Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702 article info abstract Article history: Cancer is a complex systemic disorder that affects many organs and tissues and arises from the altered function of Received 5 October 2017 multiple cellular and molecular mechanisms. One of the systems malfunctioning in cancer is the immune system. Received in revised form 18 December 2017 Restoring and improving the ability of the immune system to effectively recognize and eradicate cancer is the main Accepted 11 January 2018 focus of immunotherapy, a topic which has garnered recent and significant interest. The initial excitement about Available online 12 January 2018 immunotherapy, however, has been challenged by its limited efficacy in certain patient populations and the devel- Keywords: opment of adverse effects such as therapeutic resistance and autoimmunity. At the same time, a number of ad- fi Nanoparticles vances in the eld of nanotechnology have sought to address the challenges faced by modern Vaccines immunotherapeutics and allow these therapeutic strategies to realize their full potential. This endeavour requires Adjuvant anunderstanding ofnotonlytheimmunologicalbarriersincancerbutalsothemechanismsbywhichmoderntech- Cell therapy nologies and immunotherapeutics modulate the function of the immune system. Herein, we summarize the major Drug delivery barriers relevant to cancer immunotherapy and review current progress in addressing these obstacles using vari- ous approaches and clinically approved therapies. We then discuss the remaining challenges and how they can be addressed bynanotechnology. Welay out translational considerationsrelevant to thetherapies describedand pro- pose a framework for the development of next-generation nanotechnology-enabled immunotherapies. © 2018 Published by Elsevier B.V. Contents 1. Introduction............................................................... 4 2. Barrierstoeffectiveanti-tumorimmunotherapy............................................... 5 2.1. Biochemicalmechanismsoftumorimmuneescape.......................................... 5 2.1.1. Dysfunctionofantigen-processingmachinery........................................ 5 2.1.2. InhibitoryligandsforthecontrolofT-cellfunction...................................... 5 2.1.3. Immunosuppressivecytokinesandmediators........................................ 5 2.2. Cellularmechanismsoftumorimmuneescape............................................ 5 2.2.1. DysregulationofDCfunction................................................ 5 2.2.2. Immunosuppressivecellpopulations............................................ 6 2.3. Vascular.............................................................. 6 3. Addressingbarrierswithconventionalimmunotherapies........................................... 6 3.1. Cytokinetherapy.......................................................... 6 3.2. AdoptiveT-cellimmunotherapy................................................... 7 3.3. Chimericantigenreceptor(CAR)-Tcelltherapy............................................ 7 3.4. Checkpointinhibitors........................................................ 8 3.5. Cancervaccines.......................................................... 9 4. Addressingbarrierswithnanotechnology.................................................. 9 4.1. Directstrategiestoaddressingbarrierstoimmunotherapy....................................... 9 4.1.1. Offsetting the immunosuppressive tumor microenvironment by tumor-specificdelivery..................... 9 ⁎ Corresponding author at: Frederick National Laboratory for Cancer Research, P.O. Box B, 1050 Boyles Street, Frederick, MD 21702-1201, USA. E-mail address: [email protected] (M.A. Dobrovolskaia). https://doi.org/10.1016/j.addr.2018.01.005 0169-409X/© 2018 Published by Elsevier B.V. 4 E. Hong, M.A. Dobrovolskaia / Advanced Drug Delivery Reviews 141 (2019) 3–22 4.1.2. Buildingmoreeffectivecancervaccineswithnanotechnology..................................10 4.1.3. Influenceofnanoparticlephysicochemicalcharacteristicsonlymphnodetargeting........................10 4.1.4. Adjuvantdeliverybynanoparticles..............................................10 4.1.5. Tunableantigendeliveryforcross-presentationandsustainedrelease..............................10 4.1.6. Nanoparticlesystemsforexternallyinducedimmunotherapy..................................11 4.2. Improvingconventionalimmunotherapies..............................................12 4.2.1. Nanoparticlesforphysiologicallyrelevantcytokinedelivery..................................12 4.2.2. Enhancingadoptiveimmunotherapy.............................................13 5. Translationalconsiderations........................................................14 5.1. Lessonslearnedfrombiotherapeutics.................................................14 5.2. Lessonslearnedfromtherapeuticoligonucleotides...........................................14 5.3. Lessonslearnedfromnanotechnology-basedcombinationproductsandcomplexdrugformulations....................15 5.4. Lessonslearnedfromconventionalimmunotherapy..........................................16 6. Roadmaptothenextgenerationofnanotechnology-enabledimmunotherapies.................................16 Acknowledgments...............................................................17 References...................................................................17 1. Introduction development of resistance to immunotherapy, toxicities associated with therapies such as cytokine or CAR-T cell infusion, and the limited A successful anti-tumor immune response consists of several com- efficacy of approaches such as cancer vaccines [4–7]. New generations ponents. First, tumor-associated antigens (TAAs) must be presented to of immunotherapies will have to address these challenges to achieve effector immune cells by antigen-presenting cells (APCs), which acti- broader applicability and better patient outcomes. vate the effector cells and prepare them for an immune response. Sec- Nanotechnology offers unique opportunities to tackle the clinical ond, effector immune cells must make their way to the tumor, challenges faced by current immunotherapies. Depending on their navigate the tumor vasculature, and penetrate the tumor tissue. Finally, physicochemical characteristics, nanoparticles can alter the pharmaco- these effector cells must bind to and recognize the TAAs on the tumor kinetics, biodistribution, and activity of the therapeutic agents that are surface and kill the tumor cells presenting these antigens. This process loaded within them. These properties allow investigators to engineer is cyclical, wherein cancer cell death can release more antigens for pro- specific nanotechnology-enabled strategies for improving the therapeu- cessing by APCs and activate effector cells, thereby enhancing subse- tic efficacy of anti-cancer drugs. Several nanoparticle drugs have already quent anti-tumor activity [1]. The anti-tumor immune response, been approved for cancer therapy, such as liposomal doxorubicin however, is dysfunctional in cancer. Tumors can induce immune toler- (Doxil), albumin-bound paclitaxel (Abraxane), and liposomal ance by avoiding or blocking the immune system from recognizing irinotecan (Onivyde). In recent years, nanotechnology-enabled strate- TAAs, or by actively suppressing activated effector T cells and natural gies for immunotherapy have been extensively investigated, yielding killer (NK) cells to prevent them from eliminating tumor cells [2, 3]. new strategies and insights for the development of more effective Cancer immunotherapy aims at restoring the proper function of the next-generation immunotherapies. anti-tumor immune response by overcoming mechanisms of tumor im- In this review, we summarize the barriers facing modern immuno- mune evasion or suppression. Recent advances in immunotherapy have therapy and examine the general cellular and biochemical barriers of invigorated the field by identifying and addressing the mechanisms by the tumor microenviroment, the ways they are addressed by modern which tumors avoid being cleared by the immune system. These recent immunotherapies, and the specific barriers facing particular immuno- clinical successes and the approval of several promising immunothera- therapeutic approaches. We also discuss how nanotechnology can di- peutic drugs have spurred substantial scientific and public interest in rectly address the general barriers to generating anti-tumor immunity the field. However, the clinical application of cancer immunotherapy and help overcome the specific barriers that limit current immunother- still faces an array of challenges, including the lack of response or apies. We summarize translational considerations and lessons learned Box 1 Barriers to effective immunotherapy. Problems Mechanisms/barriers Selected references Lack of tumor antigen processing and presentation – Downregulation or loss of class I MHC [10] – Disruption of antigen-processing machinery Disabling of antigen-presenting cells in the tumor – Prevention of DC maturation
Load more

Recommended publications
  • Marriage Certificates
    GROOM LAST NAME GROOM FIRST NAME BRIDE LAST NAME BRIDE FIRST NAME DATE PLACE Abbott Calvin Smerdon Dalkey Irene Mae Davies 8/22/1926 Batavia Abbott George William Winslow Genevieve M. 4/6/1920Alabama Abbotte Consalato Debale Angeline 10/01/192 Batavia Abell John P. Gilfillaus(?) Eleanor Rose 6/4/1928South Byron Abrahamson Henry Paul Fullerton Juanita Blanche 10/1/1931 Batavia Abrams Albert Skye Berusha 4/17/1916Akron, Erie Co. Acheson Harry Queal Margaret Laura 7/21/1933Batavia Acheson Herbert Robert Mcarthy Lydia Elizabeth 8/22/1934 Batavia Acker Clarence Merton Lathrop Fannie Irene 3/23/1929East Bethany Acker George Joseph Fulbrook Dorothy Elizabeth 5/4/1935 Batavia Ackerman Charles Marshall Brumsted Isabel Sara 9/7/1917 Batavia Ackerson Elmer Schwartz Elizabeth M. 2/26/1908Le Roy Ackerson Glen D. Mills Marjorie E. 02/06/1913 Oakfield Ackerson Raymond George Sherman Eleanora E. Amelia 10/25/1927 Batavia Ackert Daniel H. Fisher Catherine M. 08/08/1916 Oakfield Ackley Irving Amos Reid Elizabeth Helen 03/17/1926 Le Roy Acquisto Paul V. Happ Elsie L. 8/27/1925Niagara Falls, Niagara Co. Acton Robert Edward Derr Faith Emma 6/14/1913Brockport, Monroe Co. Adamowicz Ian Kizewicz Joseta 5/14/1917Batavia Adams Charles F. Morton Blanche C. 4/30/1908Le Roy Adams Edward Vice Jane 4/20/1908Batavia Adams Edward Albert Considine Mary 4/6/1920Batavia Adams Elmer Burrows Elsie M. 6/6/1911East Pembroke Adams Frank Leslie Miller Myrtle M. 02/22/1922 Brockport, Monroe Co. Adams George Lester Rebman Florence Evelyn 10/21/1926 Corfu Adams John Benjamin Ford Ada Edith 5/19/1920Batavia Adams Joseph Lawrence Fulton Mary Isabel 5/21/1927Batavia Adams Lawrence Leonard Boyd Amy Lillian 03/02/1918 Le Roy Adams Newton B.
    [Show full text]
  • CONGRESSIONAL RECORD—SENATE, Vol. 155, Pt. 7 8573 ORDER for ADJOURNMENT Health Care Policies in the Senate That Do Play a Crucial Role in This Nation’S Mr
    March 25, 2009 CONGRESSIONAL RECORD—SENATE, Vol. 155, Pt. 7 8573 ORDER FOR ADJOURNMENT health care policies in the Senate that do play a crucial role in this Nation’s Mr. DURBIN. Mr. President, if there apply specifically to rural commu- mental health care. is no further business to come before nities. I am proud to join her as we These providers go through rigorous the Senate, I ask unanimous consent it fight to ensure Medicare patients liv- training, and it is similar to the cur- stand adjourned under the previous ing in rural and in frontier States have riculum of a master’s level social order following the remarks of Senator access to and a choice of their mental worker. They must not be excluded BARRASSO. health professionals. from the Medicare Program. I believe The PRESIDING OFFICER. Without The Seniors Mental Health Access S. 671 is critically important to the objection, it is so ordered. Improvement Act will permit marriage health and the well-being of our Na- Mr. DURBIN. Mr. President, I sug- and family therapists and licensed pro- tion’s seniors. It is time for this bill to gest the absence of a quorum. fessional counselors to bill Medicare become law. The PRESIDING OFFICER. The directly. These providers will then re- I yield the floor. clerk will call the roll. ceive 75 percent of the rate that psychi- f The legislative clerk proceeded to atrists and psychologists receive for the same services. ADJOURNMENT UNTIL 9:30 A.M. call the roll. TOMORROW Mr. BARRASSO. Mr. President, I ask I want my colleagues to know that S.
    [Show full text]
  • 1986 Surname
    Surname Given Age Date Page Maiden Note Abegg Missel 88 15-Dec C-8 Abernathy Manuel 79 1-Jan C-5 Abner Tom 71 24-Jun B-7 Abraham Aloysius J. 77 24-Jul C-2 Abram Harold Glenn 75 14-Sep D-2 Abramson Frances L. 46 28-Dec C-7 Levine Ackerman Mary 79 16-Sep B-7 Adam Paul T. 76 10-Sep C-5 Adams Claude 78 20-Jan A-5 Adams Gloria L. 48 23-Sep D-6 Adams Irene 77 21-Aug C-3 Adams Martha 72 3-Nov C-1 Adank Gerald C. 65 1-Dec C-8 Veteran of World War II Adkins Johnnie Lee 78 13-Feb B-9 Adley Daisy A. 93 2-Sep D-7 Ahlborn Raymond W. 73 2-May C-1 Aird Gordon R. 77 21-Nov D-1 See article, p. D-1 Aitken Marion 70 1-Jul B-7 Aksentijevic Martha 56 17-Sep B-8 Alamillo Nora 75 4-Feb C-1 Albert Lester E. 65 30-Sep B-7 Albrecht Victoria A. 84 3-Jan A-7 Aldrin Raymond E. 71 11-Aug B-5 Aleksandrovic Ivan 76 11-Dec B-13 Aleksandrovic Jelena 79 2-Dec C-1 Ales Francis J. 69 31-Mar B-8 Alexander Janet 49 28-Jul C-1 Alexander Penny C. 60 24-Mar C-1 Alexander Terry 53 9-Dec C-1 Alexander Vera (Cook) 2-Dec C-1 Alexander William A. 50 27-Dec C-2 Alfaro Mark A. 21 5-Feb D-1 Alger Kenneth H.
    [Show full text]
  • Birth Certificate Index - Black Hawk County (1909-June 1921)Q 9/5/2017
    Birth Certificate Index - Black Hawk County (1909-June 1921)Q 9/5/2017 Name Birth Date County Mother's Maiden Name Certificate # Box # Aagard, Hans Carrel 07 Oct. 1915 Black Hawk Aagard 0017 B2085 Abernethy, Bernice Irene 11 Apr. 1920 Black Hawk James 0957 B2090 Abfelter, Francis Mable 28 Nov. 1918 Black Hawk Losfte 0001 B2087 Abfelter, Ruby Esther 14 Oct. 1914 Black Hawk Lofte 0734 B2085 Abraham, Dorothy Eveline 18 Mar. 1912 Black Hawk See 0676 B2083 Abrams, Burr Raymond 06 Nov. 1909 Black Hawk Lee 0171 B2081 Abrams, Pauline Evelyn 20 Mar. 1920 Black Hawk Shafer 0838 B2090 Abrams, Thelma Doris 24 Aug. 1915 Black Hawk See 0013 B2085 Abrams, Wilma May 03 Mar. 1918 Black Hawk See 0002 B2087 Ackerman, Arlan Walter 17 July 1920 Black Hawk Westendorf 0001 B2089 Ackerman, Berdina Sopha 28 Aug. 1912 Black Hawk Tegtmeier 0151 B2082 Ackerman, Bonnie R. 22 Nov. 1916 Black Hawk Strack 0012 B2085 Ackerman, Gladys Martha 03 Oct. 1915 Black Hawk Tegtmeyer 0006 B2085 Ackerman, Harold J. 08 Jan. 1909 Black Hawk Tegtmeier 0062 B2081 Ackerman, John Henry 14 Aug. 1915 Black Hawk Burk 0011 B2085 Ackerman, Junion Douglas 09 Aug. 1917 Black Hawk Armagost 0109 B2086 Ackerman, Kenneth Howard 07 June 1920 Black Hawk Amdahl 1155 B2090 Ackerman, Mame Ann 26 June 1909 Black Hawk Kirschbaum 0382 B2081 Ackerman, Martin R. 1910 Black Hawk Stark 0090 B2081 Ackerman, Mary Lou 25 Feb. 1921 Black Hawk Dusk 0001 B2091 Ackerman, Ralph Edward 07 Oct. 1913 Black Hawk Dusk 0269 B2083 Ackerman, Vernita Irene 09 Sept. 1917 Black Hawk Dusk 0108 B2086 Ackles, Joyce Eleanor 29 Sept.
    [Show full text]
  • 04Medicine.Pdf
    117 the University at Stony Brook as well as by the School clinical affiliates of the Nassau University of Medical Center, Winthrop University Hospital, the Northport Veterans Affairs Medical Center, Medicine and various community clinical facilities integrated under a variety of arrangements. Dean: Norman H. Edelman Vice Deans: Craig C. Malbon, scientific affairs; Peter C. Admission to the MD Program Williams, academic affairs and faculty development The Medical College Admission Test (MCAT) must be taken no later than the year prior to the year for which the student seeks Associate Deans: Thomas Biancaniello, medical affairs; Jack admission. By law, applicants must have completed a mini- Fuhrer, admissions; Frederick M. Schiavone, medical educa- mum of two years of college before matriculation; however, tion; Aldustus Jordan, student and minority affairs; Michael L. medical school admissions committees favor applicants with Rainey, academic advising; Dorothy S. Lane, continuing med- more complete educational preparation. Premedical course ical education; Derinda Pell, administration and finance. requirements include one year each of biology, physics, inor- ganic chemistry and organic chemistry (all with lab), and one Associate Deans for clinical affiliations: John F. Aloia, Winthrop year of English. A basic course in biochemistry is helpful in University Hospital; Edward J.C. Mack, Veterans Affairs Med- preparing students for the first year of medical school; howev- ical Centerat Northport; Michael Mastow, Nassau University er, it is neither a requirement nor a criterion for admission. Medical Center. The school hopes to acquire a student body representative of a variety of backgrounds, experiences, and interests. The school examines rigorously the preparation and promise for Assistant Dean: Grace Agnetti, Marilyn London creative work in medicine of all applicants, and asks to meet personally with those in whom it is most seriously interested.
    [Show full text]
  • Response to Comments for the Hudson River Pcbs Superfund Site
    FINAL SECOND FIVE-YEAR REVIEW COMMENT RESPONSE FOR THE HUDSON RIVER PCBS SUPERFUND SITE Prepared by U.S. Environmental Protection Agency Region 2 April 2019 FIVE-YEAR REVIEW COMMENT RESPONSE FOR HUDSON RIVER PCBs SITE TABLE OF CONTENTS I. INTRODUCTION .............................................................................................................1 1.1 The Second Hudson River PCBs Superfund Site Five Year Review ...............................1 1.2 FYR Public Outreach and Engagement ............................................................................1 1.3 FYR Comment Review and Response ..............................................................................2 II. COMMENTS OUTSIDE SCOPE OF FYR ....................................................................12 III. MASTER COMMENTS AND RESPONSES ................................................................12 3.1 Data Collection ................................................................................................................12 3.1.1 Comment 1: Additional data are required to understand the effectiveness of the remedy.......................................................................................................................13 3.1.2 Comment 6: Consumption survey required to assess new populations eating fish ..16 3.1.3 Comment 7: Despite institutional controls people are still eating fish .....................17 3.1.4 Comment 14: EPA must reinstate suspended solids monitoring at Waterford to improve evaluation of PCB load to the Lower
    [Show full text]
  • 2016–17 Commencement Program
    COMMENCEMENT UNIVERSITY OF COLORADO BOULDER FOLSOM STADIUM MAY 12, 2017 One Hundred Forty-First Year of the University CommCoverMay2017 update.indd 1 3/23/17 11:01 AM Norlin Charge to the Graduates The first commencement at the University of Colorado was held for six graduates on June 8, 1882, in the chapel of Old Main. It was not until 40 years later, on September 4, 1922, that the first summer commencement was held. Since the first commencement in 1882, the University of Colorado Boulder has awarded 350,000 degrees. The traditional Norlin Charge to the graduates was first read by President George Norlin to the June 1935 graduating class. You are now certified to the world at large as alumni of the university. She is your kindly mother and you her cherished sons and daughters. This exercise denotes not your severance from her, but your union with her. Commencement does not mean, as many wrongly think, the breaking of ties and the beginning of life apart. Rather it marks your initiation in the fullest sense into the fellowship of the university, as bearers of her torch, as centers of her influence, as promoters of her spirit. The university is not the campus, not the buildings on campus, not the faculties, not the students of any one time—not one of these or all of them. The university consists of all who come into and go forth from her halls, who are touched by her influence, and who carry on her spirit. Wherever you go, the university goes with you.
    [Show full text]
  • 2001 Birkebeiner Men's Results
    2001 Birkebeiner Men's Results CLASS 25% PACE RANK TIME BIB NAME HOMETOWN STATE NATION CLASS RANK CLUB (mn/km) 1 2:32:53.5 202 GIANANTONIO ZANETEL MOENA ITA M 30-34 1 Y 2.59 2 2:32:55.3 3 STEPHANE PASSERON GAP FRA M 30-34 2 Y 2.59 3 2:33:03.1 206 FAUSTINO BORDIGA MOENA ITA M 30-34 3 Y 3 4 2:33:59.5 207 PIERLUIGI COSTANTIN MOENA ITA M 25-29 1 Y 3.01 5 2:34:01.5 4 STANISLAV REZAC JADLOWIC NAD WI CZ M 25-29 2 Y 3.01 6 2:34:10.0 19 ROY DIDIER M 30-34 4 Y 3.01 7 2:34:19.9 7 NATHAN L SCHULTZ BOULDER CO USA M 25-29 3 Y 3.01 8 2:34:47.8 52 JOHN BAUER DULUTH MN USA M 30-34 5 Y 3.02 9 2:35:05.9 203 OTHMARR PIDER MOENA ITA M 30-34 6 Y 3.02 10 2:36:32.1 205 ANDREA PICCOLIORI MOENA ITA M 19-24 1 Y 3.04 11 2:36:33.9 78 DAVE STEWART RIPTON VT USA M 19-24 2 Y 3.04 12 2:37:17.8 156 PATRICK N WEAVER BEND OR USA M 30-34 7 Y 3.05 13 2:37:29.9 8 PETE F VORDENBERG BOZEMAN MT USA M 25-29 4 Y 3.05 14 2:37:38.5 41 PHILIP A BOWEN GRAND MARAIS MN USA M 25-29 5 Y 3.05 15 2:38:09.5 5 MARC GILBERTSON HYDE PARK VT USA M 30-34 8 Y 3.06 16 2:39:04.4 26 BRUCE L BAUER DULUTH MN USA M 25-29 6 Y 3.07 17 2:39:29.8 204 MARCO CATTANEO MOENA ITA M 25-29 7 Y 3.07 18 2:41:31.0 13 VITALI TCHERNOV KHABAROVSK RUS M 25-29 8 Y 3.1 19 2:42:16.3 163 SCOTT LOOMIS PARK CITY UT USA M 25-29 9 Y 3.1 20 2:42:29.6 179 VITALY BUROV ST PETERSBURG RUS M 19-24 3 Y 3.11 21 2:42:41.3 42 CHAD T GIESE MORA MN USA M 19-24 4 Y 3.11 22 2:44:43.4 28 ANDY J WEDDLE GREEN BAY WI USA M 19-24 5 Y 3.13 23 2:44:45.7 38 THOMAS R KRENZ OSCEOLA WI USA M 35-39 1 Y 3.13 24 2:44:51.4 86 KRAIG J KOSKI LONGMONT CO USA
    [Show full text]
  • Istituto Italiano Per Gli Studi Filosofici
    ISTITUTO ITALIANO PER GLI STUDI FILOSOFICI 1 2 ISTITUTO ITALIANO PER GLI STUDI FILOSOFICI La dimensione internazionale dell’Istituto Italiano per gli Studi Filosofici Napoli 2010 3 A cura di MARIASOLE FANUZZI e ANTONIO GARGANO con la collaborazione di ANTONELLA CHIARO Stampato nel mese di luglio MMX Arti Grafiche Cecom srl - Bracigliano (Sa) © Istituto Italiano per gli Studi Filosofici Palazzo Serra di Cassano Via Monte di Dio 14, Napoli www.iisf.it ISBN 978-88-89946-00-8 4 Свобода исследования и преподавания и назначение государственного университета Исполнившееся первое десятилетие со дня рождения Итальянского института философских исследований побуждает нас задать себе некоторые вопросы, в том числе и в связи с недавними спорами относительно назначения и действенности культурных институций, основанных и поддерживаемых частными лицами, относительно права таких заведений на получение помощи со стороны государства, а значит, и относительно собственной роли университетов, какой она является нам во всех отраслях естественного, научного и гуманитарного познания. Успех и большой общественный резонанс культурных инициатив Института, основанного в Неаполе Джерардо Мароттой, а также связанной с Институтом Высшей школы гуманитарных и естественных наук, показывают, что оба учреждения отвечают неудовлетворенным потребностям множества людей, испытывающих тягу к знаниям и наделенных критическим складом ума, причем отвечают им по меньшей мере столь же успешно, как и другие заведения, преследующие сходные цели, но возникшие значительно раньше и существующие полностью на государственном содержании. В этом легко убедиться, стоит лишь освободиться – что, впрочем, случается нечасто, – от некоторых «идолов площади», которые вынуждают нас видеть в университетских и академических институциях, равно как и в иных государственных «органах науки», естественные и самородные очаги научного * Статья Джованни Пульезе Каррателли, опубликованная в специальном выпуске журнала «La Provincia di Napoli» 3/4 1987, посвященном Итальянскому институту философских исследований.
    [Show full text]
  • Last Name First Name Middle Name Birth Date Death Date Aach Herb
    AA/PG Library - Corcoran Gallery of Art - Artist Vertical File Collection, Spring 2016 Last name First name Middle name Birth date Death date Aach Herb 1923 1985 Aalto Alvar 1899 1976 Aaron David Aarons George 1896 1980 Abadi Fritzie 1915 Abanavas Constantine 1922 Abbey Edward Austin 1852 1911 Abbot Edith R. 1876 1964 Abbot John 1751 1840 Abbott Elenore 1875 1935 Abbott Lillian Moore 1870 1944 Abbott Mary Odgen Abbott S. N. 1874 1954 Abbott Yarnall 1870 1938 Abbott-Ryan Pat Abdell Douglas 1947 Abdy Rowena Meeks 1887 1945 Abel Louise 1894 Abel Myer 1904 1948 Abeles Kim Victoria 1952 Abercrombie Gertrude Abish Cecile 1930 Abrahamsen Christian 1887 1983 Abramofsky Israel 1888 1975 Abramovitz Albert Abramowitz Benjamin 1917 2011 Abrams Lucien 1870 1941 Abrams Ross Abrams Ruth 1912 1986 Acconci Vito 1940 Acheson Alice Stanley 1895 1996 Ackerman Harry Gregory 1909 1988 Ackroyd Norman 1938 Adams Amy Addams Clifford Isaac 1876 1942 Adams Herbert 1850 1901 Adams J. Ottis 1851 1927 Adams Katherine Langhorne 1883 1977 Adams Kenneth M. 1897 1966 Adams Mac 1943 Adams Pat 1928 Adams Robert 1917 1984 Adams Wayman 1883 1959 Adamson David Addams Charles 1912 1988 Addison Wilfred John Ades Josiah 1899 Adickes David 1927 Adler Gwen Adler Jankel 1895 1949 Adler Lee 1934 Adler Samuel 1901 1980 Adnan Etel 1925 Adomeit George G. 1879 1967 Adrian (Gilbert) 1903 1959 Agam Yaacov 1928 Agard Jim Agnew G. Harvey 1895 1971 Agostini Peter Ahrens Ellen Wetherald 1859 1938 Aid George C. 1872 1938 Aiken Charles Avery 1872 1965 Aiken William H. 1934 Aitchison-Walker Jessie Aitken Robert Ingersoll 1878 1949 Aitken Russell Barnett 1910 2002 Ajay Abe 1919 Akeley Carl Ethan 1864 1926 Akers Benjamin Paul 1825 1861 Akin Louis B.
    [Show full text]
  • Physcian Directory Coney Island Health Professional by License And
    NYC Health + Hospitals Physcian Directory Corporate Finance Coney Island Updated as of March 25, 2016 Health Professional By License and NPI FACILITY NAME DOCTOR LAST NAME DOCTOR FIRST NAME Coney Island AANONSEN DEBORAH Coney Island AARON ROBERT Coney Island ABAYEV ZURAB Coney Island ABBERBOCK GARY Coney Island ABBOUD AIMAN Coney Island ABDELSHAFYABDEL NULL Coney Island ABDELSHAFYIBRAHM NULL Coney Island ABDUL WAHID Coney Island ABDULLAH MUHAMMAD Coney Island ABEDIN RASHED Coney Island ABI FADEL Coney Island ABRAHAM SASHA Coney Island ABRAHAMS MICHAEL Coney Island Abraitis Stephanie Coney Island ABRAMOV ALEXANDR Coney Island ABRAMOV MICHAEL Coney Island ABRAMOVA INNA Coney Island ABRAMOVICH GALINA Coney Island ABRAMSON ALLA Coney Island ABRASS ANDREW Coney Island ABUELENIN DANIEL Coney Island ACHARYA NIKHIL Coney Island ACOSTA MICHELLE Coney Island ADAMS FRANCIS Coney Island ADAMS LAUREN Coney Island ADANIEL TINDALO Page 1 of 136 NYC Health + Hospitals Physcian Directory Corporate Finance Coney Island Updated as of March 25, 2016 Health Professional By License and NPI FACILITY NAME DOCTOR LAST NAME DOCTOR FIRST NAME Coney Island ADDEO JOSEPH Coney Island ADDEPALLI RAJ Coney Island ADEDEJI ADEDAYO Coney Island ADEISHVILI GRIGOL Coney Island ADEYEMI BABATUNDE Coney Island ADIMOOLAM SEETHARAMAN Coney Island ADLER MAYER Coney Island ADLER ROBERT Coney Island ADZIMAH JOSEPH Coney Island AFROZE SALMA Coney Island AFSHARI MICHAEL Coney Island AGABEKIAN TATIANA Coney Island AGARONOV VITALIY Coney Island AGARWAL SHEENU Coney Island AGAYEVA KAMILA
    [Show full text]
  • Marriage-Officiants-May-8-2015.Pdf
    Religious Marriage Officiants listed by Municipality, Name, and Religious Body Célébrants de mariage religieux listés par municipalité, nom, et organisme religieux Date last updated: May 8, 2015 Date de dernière mise à jour : 8 mai 2015 Note: registrations and cancellations of religious marriage officiants are generally updated within 4 weeks of notification from Religious Bodies Remarque : les inscriptions et les radiations des célébrants de mariage religieux sont généralement mises à jour dans les quatre semaines suivant l’avis de la part d’organismes religieux. Municipality, Name, Religious Body Municipalité, nom, organisme religieux Acton, Benham, John James L, Hamilton Conference - United Church Acton, Chaffey, Robert, Clergy Support Memorial Church Acton, Cho, Hyuk, Toronto Conference - United Church Acton, Dykxhoorn, Jeff, The Christian And Missionary Alliance Central Canada District Acton, Feth, Kersten, Partners In Harvest (Canada) Acton, Hetu, Robert J, Roman Catholic Diocese Of Hamilton Acton, Letki, Matthew, Clergy Support Memorial Church Acton, Mclean, Duane Donald, Canadian Fellowship Of Churches And Ministers Acton, Nelson, Todd Acton, Park, Jung-Hee, Toronto Conference - United Church Acton, Rennie, Gerald Acton, Roberts, Samuel Baxter, Salvation Army Acton, Roberts, Shirley, Salvation Army Acton, Simpson, Richard M, Jehovah's Witnesses Acton, Stanley, Richard Lee, The Christian And Missionary Alliance Central Canada District Acton, Van Harten, Pieter Acton, Vander Kooij, H Raymond Acton, Widdowson, Robert, Hamilton Conference
    [Show full text]