Title:
METHODS OF INDUCING IMMUNE TOLERANCE USING IMMUNOTMETHODS OF INDUCING IMMUNE TOLERANCE USING IMMUNOTOXINS OXINS
Document Type and Number:
WIPO Patent Application WO1996032137
Kind Code:
A3
Abstract:
Provided is a method of treating an immune system disorder not involving T-cell proliferation, comprising administering to the animal an immunotoxin comprising a mutant diphtheria toxin moiety linked to an antibody moiety which routes by the anti-CD3 pathway, or derivatives thereof under conditions such that the disorder is treated. Thus, the present method can treat graft-versus-host disease. Also provided is a method of inhibiting a rejection response by inducing immune tolerance in a recipient to a foreign mammalian donor tissue or cells, comprising the steps of: a) exposing the recipient to an immunotoxin so as to reduce the recipients' peripheral blood T-cell lymphocyte population by at least 80 %, wherein the immunotoxin is anti-CD3 antibody linked to a diphtheria protein toxin, wherein the protein has a binding site mutation; and b) transplanting the donor cells into the recipient, whereby a rejection response by the recipient to the donor organ cell is inhibited, and the host is tolerized to the donor cell.
Inventors:
KNECHTLE STUART J (US)
NEVILLE DAVID A (US)
SCHARFF JOSHUA E (US)
THOMAS JUDITH (US)
NEVILLE DAVID A (US)
SCHARFF JOSHUA E (US)
THOMAS JUDITH (US)
Application Number:
PCT/US1996/005087
Publication Date:
January 09, 1997
Filing Date:
April 12, 1996
Export Citation:
Assignee:
US HEALTH (US)
UNIV ALABAMA RES FOUND (US)
KNECHTLE STUART J (US)
NEVILLE DAVID A (US)
SCHARFF JOSHUA E (US)
THOMAS JUDITH (US)
UNIV ALABAMA RES FOUND (US)
KNECHTLE STUART J (US)
NEVILLE DAVID A (US)
SCHARFF JOSHUA E (US)
THOMAS JUDITH (US)
International Classes:
A61K31/365; A61K31/57; A61K35/12; A61K35/14; A61K35/28; A61K38/05; A61K38/13; A61K39/395; A61K47/48; C07K14/34; C07K16/12; C07K16/28; C07K16/44; C07K16/46; A61K38/00; (IPC1-7): A61K47/48; A61K35/14; A61K35/12; A61K31/57; A61K31/365; A61K38/13; A61K39/05
Domestic Patent References:
| WO1992013562A1 | 1992-08-20 | |||
| WO1984000382A1 | 1984-02-02 |
Foreign References:
| EP0616034A2 | 1994-09-21 |
Other References:
D. NEVILLE ET AL.: "Anti-T cell immunotoxins: a look at post-endocytotic receptor-mediated routing.", JOURNAL OF CONTROLLED RELEASE, vol. 24, no. 1-3, 1993, AMSTERDAM, THE NETHERLANDS, pages 133 - 144, XP000303922
D. NEVILLE ET AL.: "In vivo T-cell ablation by a holo-immunotoxin directed at human CD3.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE USA, vol. 89, no. 7, 1 April 1992 (1992-04-01), WASHINGTON, DC, USA, pages 2585 - 2589, XP002012195
D. NEVILLE ET AL.: "Enhancement of immunotoxin efficacy by acid-cleavable cross-linking agents utilizing diphteria toxin and toxin mutants.", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 264, no. 25, 5 September 1989 (1989-09-05), BALTIMORE, MD, USA, pages 14653 - 14661, XP002012196
D. HULLETT ET AL.: "DAB486-IL-2 (IL-2-toxin) in combination with low dose RS-61443 (mycophenolate mofetil) prolongs murine thyroid allograft survival.", TRANSPLANTATION PROCEEDINGS, vol. 25, no. 1, February 1993 (1993-02-01), NEW YORK, NY, USA, pages 756 - 757, XP000579774
J. THOMPSON ET AL.: "An anti-CD3 single-chain immunotoxin with a truncated diphteria toxin avoids inhibition by pre-existing antibodies in human blood.", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 270, no. 47, 24 November 1995 (1995-11-24), BALTIMORE, MD, USA, pages 28037 - 28041, XP002012197
D. NEVILLE ET AL.: "A new reagent for the induction of T-cell depletion, anti-CD3-CRM9.", JOURNAL OF IMMUNOTHERAPY, vol. 19, no. 2, March 1996 (1996-03-01), HAGERSTOWN, MD, USA, pages 85 - 92, XP002012198
D. NEVILLE ET AL.: "In vivo T-cell ablation by a holo-immunotoxin directed at human CD3.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE USA, vol. 89, no. 7, 1 April 1992 (1992-04-01), WASHINGTON, DC, USA, pages 2585 - 2589, XP002012195
D. NEVILLE ET AL.: "Enhancement of immunotoxin efficacy by acid-cleavable cross-linking agents utilizing diphteria toxin and toxin mutants.", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 264, no. 25, 5 September 1989 (1989-09-05), BALTIMORE, MD, USA, pages 14653 - 14661, XP002012196
D. HULLETT ET AL.: "DAB486-IL-2 (IL-2-toxin) in combination with low dose RS-61443 (mycophenolate mofetil) prolongs murine thyroid allograft survival.", TRANSPLANTATION PROCEEDINGS, vol. 25, no. 1, February 1993 (1993-02-01), NEW YORK, NY, USA, pages 756 - 757, XP000579774
J. THOMPSON ET AL.: "An anti-CD3 single-chain immunotoxin with a truncated diphteria toxin avoids inhibition by pre-existing antibodies in human blood.", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 270, no. 47, 24 November 1995 (1995-11-24), BALTIMORE, MD, USA, pages 28037 - 28041, XP002012197
D. NEVILLE ET AL.: "A new reagent for the induction of T-cell depletion, anti-CD3-CRM9.", JOURNAL OF IMMUNOTHERAPY, vol. 19, no. 2, March 1996 (1996-03-01), HAGERSTOWN, MD, USA, pages 85 - 92, XP002012198
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