Development of ImmTOR Tolerogenic Nanoparticles for the Mitigation of Anti-drug Antibodies.

Frontiers in Immunology
Takashi Kei Kishimoto

Abstract

The development of anti-drug antibodies (ADAs) is a common cause for treatment failure and hypersensitivity reactions for many biologics. The focus of this review is the development of ImmTOR, a platform technology designed to prevent the formation of ADAs that can be applied broadly across a wide variety of biologics by inducing immunological tolerance with ImmTOR nanoparticles encapsulating rapamycin. The induction of tolerance is antigen-specific and dependent on the incorporation of rapamycin in nanoparticles and the presence of the antigen at the time of administration of ImmTOR. Evidence for the induction of specific immune tolerance vs. general immune suppression is supported by the findings that: (1) ImmTOR induces regulatory T cells specific to the co-administered antigen; (2) tolerance can be transferred by adoptive transfer of splenocytes from treated animals to naïve recipients; (3) the tolerance is durable to subsequent challenge with antigen alone; and (4) animals tolerized to a specific antigen are capable of responding to an unrelated antigen. ImmTOR nanoparticles can be added to new or existing biologics without the need to modify or reformulate the biologic drug. The ability of ImmTOR to mitigate the formation...Continue Reading

References

Jan 1, 1994·Annual Review of Immunology·P Matzinger
Feb 1, 1997·Transplantation Proceedings·B D Kahan
Jun 25, 1998·Current Opinion in Immunology·M K Slifka, R Ahmed
Jun 8, 2001·Proceedings of the National Academy of Sciences of the United States of America·C A Janeway
Feb 15, 2002·The New England Journal of Medicine·Nicole CasadevallPatrick Mayeux
Nov 5, 2002·Current Opinion in Immunology·Pamela S Ohashi, Anthony L DeFranco
Mar 5, 2003·Annual Review of Immunology·Ralph M SteinmanMichel C Nussenzweig
May 6, 2004·The Journal of Pediatrics·Priya Sunil Kishnani, R Rodney Howell
Mar 5, 2005·Blood·Manuela BattagliaMaria-Grazia Roncarolo
Oct 6, 2005·Annals of Internal Medicine·Hyon K ChoiUNKNOWN American Physiological Society
Mar 15, 2006·Journal of Controlled Release : Official Journal of the Controlled Release Society·Sai T ReddyMelody A Swartz
Jun 29, 2006·Annals of the New York Academy of Sciences·Gerald PfisterBeatrix Grubeck-Loebenstein
Mar 19, 2008·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Katherine F Croom, Paul L McCormack
Apr 5, 2008·European Journal of Immunology·Vania ManolovaMartin F Bachmann
Nov 26, 2008·Handbook of Experimental Pharmacology·Ryan FischerAngus W Thomson
Jul 9, 2009·Journal of Thrombosis and Haemostasis : JTH·S NayakR W Herzog
Sep 25, 2009·Molecular Genetics and Metabolism·Priya S KishnaniY-T Chen
Oct 31, 2009·Nature Reviews. Drug Discovery·Michael Goodman
Oct 1, 2010·Nature Reviews. Rheumatology·Charlotte L M KrieckaertGerrit-Jan Wolbink
Nov 9, 2010·Advances in Immunology·Roberto A Maldonado, Ulrich H von Andrian
Jan 20, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Amit C NathwaniAndrew M Davidoff
Feb 15, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ryan D MichalekJeffrey C Rathmell
Apr 14, 2011·JAMA : the Journal of the American Medical Association·Geertje M BarteldsGerrit Jan Wolbink
May 19, 2011·Journal of Thrombosis and Haemostasis : JTH·B MoghimiR W Herzog
Jun 4, 2011·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Suhrad G BanugariaPriya S Kishnani
Oct 7, 2011·Neurology·M S FreedmanUNKNOWN MAESTRO-01 Investigators
Jan 13, 2012·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Yoav H MessingerPriya S Kishnani
Jan 27, 2012·Frontiers in Microbiology·Sushrusha NayakRoland W Herzog
Feb 23, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Fabienne DanhierVéronique Préat
Mar 13, 2012·The AAPS Journal·Narendra ChirmuleBernd Meibohm
Jan 4, 2013·Haemophilia : the Official Journal of the World Federation of Hemophilia·R Kruse-Jarres
Feb 13, 2013·Nature Reviews. Rheumatology·Pauline A van SchouwenburgGerrit Jan Wolbink
Mar 29, 2013·Nature Reviews. Drug Discovery·Jean G SathishB Kevin Park
Apr 19, 2013·Blood·Federico Mingozzi, Katherine A High
Apr 1, 2014·The AAPS Journal·Ashwin ParenkyValerie Quarmby
Apr 10, 2014·Immunological Reviews·Deepali V Sawant, Dario A A Vignali
Apr 30, 2014·International Journal of Immunopathology and Pharmacology·G LapadulaC Salvarani
Sep 16, 2014·Frontiers in Immunology·Duncan HowieStephen Cobbold
Dec 31, 2014·Proceedings of the National Academy of Sciences of the United States of America·Roberto A MaldonadoTakashi Kei Kishimoto

❮ Previous
Next ❯

Citations

Dec 16, 2020·Nature Reviews. Rheumatology·Vibeke StrandJohn D Isaacs
Mar 12, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Bernard Doger de Spéville, Victor Moreno
Jun 12, 2021·Frontiers in Immunology·Petr O IlyinskiiTakashi Kei Kishimoto
Jun 27, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Enrico Mastrobattista
Aug 14, 2021·Emerging Topics in Life Sciences·Carsten Brunn, Takashi Kei Kishimoto
Nov 17, 2021·Expert Opinion on Biological Therapy·Steven W PipeOscar G Segurado

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic

Clinical Trials Mentioned

NCT02648269
NCT02959918

Software Mentioned

nTreg
ImmTOR

Related Concepts

Related Feeds

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.