PMID: 15383608Sep 24, 2004Paper

Induction of immunological tolerance/hyporesponsiveness in baboons with a nondepleting CD4 antibody

The Journal of Immunology : Official Journal of the American Association of Immunologists
Dawn Winsor-HinesPaul D Ponath

Abstract

Tolerance induction with anti-CD4 Abs is well established in rodent transplant and autoimmune disease models, but has yet to be demonstrated in non-human primates or in clinical studies. In retrospect, failure of anti-CD4 Abs to induce tolerance in primates may be technical, a consequence of insufficient dosing and Ab properties influencing immunogenicity and cell depletion. To circumvent these possible limitations, we constructed a novel anti-CD4 mAb, TRX1, humanized to reduce immunogenicity and Fc-modified to prevent cell depletion. Using equine immune globulin (equine Ig) as a model Ag, we examined the tolerance-inducing capacity of TRX1 in baboons. During the induction phase, TRX1 inhibited the humoral response to equine Ig in a dose-dependent manner, with complete suppression of response at the highest dose tested (40 mg/kg). Upon challenge, anti-equine Ig responses were generated in baboons treated with 1 and 10 mg/kg doses of TRX1 and in control animals. In higher dosing cohorts (20 and 40 mg/kg), however, the immune response to equine Ig was modulated in seven of nine animals, including complete unresponsiveness to Ag challenges in two animals. Five of nine were hyporesponsive to equine Ig, generating titers 50- to 250-...Continue Reading

References

Dec 1, 1990·European Journal of Immunology·S X QinH Waldmann
Aug 1, 1987·European Journal of Immunology·S QinH Waldmann
Dec 1, 1989·The Journal of Experimental Medicine·M BrüggemannM S Neuberger
Mar 1, 1989·The Journal of Experimental Medicine·S X QinH Waldmann
Jul 1, 1988·The Journal of Trauma·G J JurkovichP W Curreri
Jul 1, 1995·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·A Casadevall, M D Scharff
Jan 19, 1995·The New England Journal of Medicine·C L MackallS M Steinberg
Mar 27, 1994·Transplantation·J A PowelsonA B Cosimi
Feb 12, 1993·Science·S QinH Waldmann
Dec 15, 1996·Transplantation·S E MarshallH Waldmann
Aug 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·J M PhillipsA Cooke
Sep 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·D C TsitouraD T Umetsu
Feb 15, 2001·Annals of Emergency Medicine·R C Dart, J McNally
Jul 7, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·U GrohmannP Puccetti
Jun 19, 2002·The Journal of Experimental Medicine·Luis GracaHerman Waldmann
Jan 18, 2003·Science·Chandrashekhar Pasare, Ruslan Medzhitov
Mar 27, 2003·Nature Reviews. Immunology·Jeffrey A Bluestone, Abul K Abbas
Jan 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mahzuz KarimKathryn J Wood
May 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stephen P CobboldHerman Waldmann

❮ Previous
Next ❯

Citations

Sep 22, 2006·Annual Review of Medicine·E William St ClairJeffrey Bluestone
Jul 5, 2006·International Reviews of Immunology·Lucienne Chatenoud
Aug 15, 2008·Biotechnology Journal·Sigrid R RuulsPaul W H I Parren
Oct 26, 2012·Human Vaccines & Immunotherapeutics·Leslie P CousensAnne S De Groot
Jun 2, 2006·Springer Seminars in Immunopathology·Paul Hasler
Jan 19, 2012·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Emanuela LacanáAmy S Rosenberg
Sep 21, 2012·Expert Review of Clinical Immunology·Suhrad G BanugariaPriya S Kishnani
Dec 13, 2018·ILAR Journal·Jeffrey L PlattJorge A Piedrahita
Sep 9, 2005·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Stephen P Cobbold
Nov 26, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·S C JuvetA Bushell
Dec 24, 2005·Expert Opinion on Biological Therapy·Caroline Johnson-LégerAmanda E I Proudfoot
Nov 11, 2014·Human Gene Therapy·Sang-Oh HanDwight Koeberl
Oct 12, 2016·Microbiology Spectrum·Herman WaldmannStephen Cobbold
Jan 24, 2006·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Samuel TroadecThierry Chardès

❮ Previous
Next ❯

Related Concepts

Related Feeds

Babesiosis

Babesiosis is caused by parasites of the genus babesia, which are transmitted in nature by the bite of an infected tick. Discover the latest research on babesiosis here.

Antibody Engineering

Antibody engineering technologies are constantly advancing to improve the clinical effectiveness of monoclonal and bispecific antibodies. Discover the latest research on Antibody Engineering here.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Related Papers

The Journal of Immunology : Official Journal of the American Association of Immunologists
P M WallaceP S Linsley
The Journal of Immunology : Official Journal of the American Association of Immunologists
Jiri MesteckyCharles O Elson
The Journal of Immunology : Official Journal of the American Association of Immunologists
J J Goronzy, C M Weyand
© 2021 Meta ULC. All rights reserved