Delving into the Latest Updates on A-dmDT390-bisFv(National Institutes of Health) with Synapse

Overview

Basic Info

Drug Type

Antibody toxin conjugate

Synonyms

A-dmDT390-anti-CD3 immunotoxin, Anti-CD3 antibody-diphtheria toxin conjugate, Anti-CD3 bivalent antibody-diphtheria toxin conjugate

+ [9]

Target

CD3

Action

inhibitors

Mechanism

CD3 inhibitors(T cell surface glycoprotein CD3 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [1]

Active Indication

Cutaneous T-Cell LymphomaGraft vs Host DiseaseSolid tumor

Inactive Indication

Metastatic melanomaMycosis FungoidesSezary Syndrome+ [1]

Originator Organization

National Institutes of Health

Active Organization

Virogen Biotechnology, Inc.

Inactive Organization

University of Louisville

Angimmune LLC

License Organization

Angimmune LLCVirogen Biotechnology, Inc.

Drug Highest PhasePhase 2

First Approval Date-

RegulationFast Track (United States), Orphan Drug (United States)

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Structure/Sequence

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Sequence Code 9468850

This study evaluates the effectiveness of adding a single four-day treatment of the fusion protein A-dmDT390-bisFv(UCHT1) - plus single palliative tumor radiation - with standard of care KEYTRUDA (Pembrolizumab) therapy for the treatment of metastatic melanoma. The results will be measured by comparing the combined therapy to historical data of KEYTRUDA alone.

Start Date01 Jan 2017

Sponsor / Collaborator

Angimmune LLC

NCT02943642

/ Unknown statusPhase 2

Safety and Effectiveness of A-dmDT390-bisFv(UCHT1) Fusion Protein (Resimmune®) in Subjects With Mycosis Fungoides: A Phase II Multi-center Randomized Clinical Trial

This study evaluates the effectiveness - as judged by complete response - of a single four-day treatment with the fusion protein A-dmDT390-bisFv(UCHT1) compared to oral Zolinza (Vorinostat), in a randomized 2-arm trial after a maximum of 12 months of treatment. Patient eligibility is stage IB/IIB mycosis fungoides with mSWAT < 50 who have never had lymphoid disease or a prior bone marrow / HSCT transplant.

Start Date01 Jan 2017

Sponsor / Collaborator

Angimmune LLC

[+16]

NCT01888081

/ TerminatedPhase 1/2

Phase I/II Trial of A-dmDT390-bisFv(UCHT1) Fusion Protein in Combination With Ionizing Radiation for the Treatment of Stage IV Melanoma

The purpose of this trial is to study A-dmDT390-bisFv(UCHT1) in combination with ionizing irradiation for the treatment of stage IV melanoma, a disease that is essentially incurable with median overall survival periods that range from 8-16 months.

Start Date01 Feb 2014

Sponsor / Collaborator

Angimmune LLC

[+1]

100 Clinical Results associated with A-dmDT390-bisFv(National Institutes of Health)

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100 Translational Medicine associated with A-dmDT390-bisFv(National Institutes of Health)

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100 Patents (Medical) associated with A-dmDT390-bisFv(National Institutes of Health)

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6

Literatures (Medical) associated with A-dmDT390-bisFv(National Institutes of Health)

01 Jun 2015·HaematologicaQ1 · MEDICINE

Resimmune, an anti-CD3 recombinant immunotoxin, induces durable remissions in patients with cutaneous T-cell lymphoma

Q1 · MEDICINE

Article

Author: Neville, David M ; Foss, Francine M ; Woo, Jung H ; Ahn, Chul ; Duvic, Madeleine ; Neville, Paul H ; Frankel, Arthur E

Resimmune is a second-generation recombinant immunotoxin composed of the catalytic and translocation domains of diphtheria toxin fused to two single chain antibody fragments reactive with the extracellular domain of CD3ε. We gave intravenous infusions of Resimmune 2.5 - 11.25 μg/kg over 15 minutes to 30 patients (25 with cutaneous T-cell lymphoma, 3 with peripheral T-cell lymphoma, 1 with T-cell large granular lymphocytic leukemia and 1 with T-cell prolymphocytic leukemia) in an inter-patient dose escalation trial. The most common adverse events were fever, chills, hypotension, edema, hypoalbuminemia, hypophosphatemia, and transaminasemia. Among the 25 patients with cutaneous T-cell lymphoma, there were nine responses for a response rate of 36% (95% CI, 18%-57%) including four complete remissions (16%, 95% CI, 5%-36%). The durations of the complete remissions were 72+, 72+, 60+ and 38+ months. There were five partial remissions lasting 3, 3, 3+, 6+ and 14 months. Of 17 patients with a modified skin weighted assessment tool score <50, 17 patients with stage IB/IIB, and 11 patients with both a score <50 and stage IB/IIB, nine (53%), eight (47%), and eight (73%) had responses, respectively. Further studies of Resimmune in patients with low tumor burden, stage IB-IIB cutaneous T-cell lymphoma are warranted. This trial is registered at clinicaltrials.gov as #NCT00611208.

15 Oct 2008·Journal of VirologyQ2 · MEDICINE

The Quality of Chimpanzee T-Cell Activation and Simian Immunodeficiency Virus/Human Immunodeficiency Virus Susceptibility Achieved via Antibody-Mediated T-Cell Receptor/CD3 Stimulation Is a Function of the Anti-CD3 Antibody Isotype

Q2 · MEDICINE

Article

Author: McKinney, Brett A. ; Bibollet-Ruche, Frederic ; Kutsch, Olaf ; Wagner, Frederic H. ; Ansari, Aftab A. ; Duverger, Alexandra

ABSTRACTWhile human immunodeficiency virus type 1 (HIV-1) infection is associated with hyperimmune activation and systemic depletion of CD4+T cells, simian immunodeficiency virus (SIV) infection in sooty mangabeys or chimpanzees does not exhibit these hallmarks. Control of immune activation is thought to be one of the major components that govern species-dependent differences in the disease pathogenesis. A previous study introduced the idea that the resistance of chimpanzees to SIVcpz infection-induced hyperimmune activation could be the result of the expression of select sialic acid-recognizing immunoglobulin (Ig)-like lectin (Siglec) superfamily members by chimpanzee T cells. Siglecs, which are absent on human T cells, were thought to control levels of T-cell activation in chimpanzees and were thus suggested as a cause for the pathogenic differences in the course of SIVcpz or HIV-1 infection. As in human models of T-cell activation, stimulation had been attempted using an anti-CD3 monoclonal antibody (MAb) (UCHT1; isotype IgG1), but despite efficient binding, UCHT1 failed to activate chimpanzee T cells, an activation block that could be partially overcome by MAb-induced Siglec-5 internalization. We herein demonstrate that anti-CD3 MAb-mediated chimpanzee T-cell activation is a function of the anti-CD3 MAb isotype and is not governed by Siglec expression. While IgG1 anti-CD3 MAbs fail to stimulate chimpanzee T cells, IgG2a anti-CD3 MAbs activate chimpanzee T cells in the absence of Siglec manipulations. Our results thus imply that prior to studying possible differences between human and chimpanzee T-cell activation, a relevant model of chimpanzee T cell activation needs to be established.

01 Aug 2008·Cancer Immunology, ImmunotherapyQ2 · MEDICINE

Preclinical studies in rats and squirrel monkeys for safety evaluation of the bivalent anti-human T cell immunotoxin, A-dmDT390–bisFv(UCHT1)

Q2 · MEDICINE

Article

Author: Neville, David M. Jr ; Lee, Yu-Jen ; Liu, Jen-Sing ; Kang, Soo Hyun ; Frankel, Arthur E. ; Park, Seong Kyu ; Dang, Tony ; Woo, Jung Hee ; Bour, Sarah H. ; Andreas, Elissa

The bivalent anti-human T cell immunotoxin A-dmDT390-bisFv(UCHT1) for treatment of patients with T cell malignancies is a single chain fusion protein composed of the catalytic domain and translocation domains of diphtheria toxin fused to two tandem sFv molecules reactive with human CD3 epsilon. This immunotoxin selectively kills CD3 epsilon positive T cells. To determine the maximum tolerated dose (MTD), pharmacokinetics and immunogenicity of A-dmDT390-bisFv(UCHT1), rat and squirrel monkey studies were performed. In both animal studies, animals received either 0, 2.5 (low), 25 (medium), or 56.25 microg/kg (high) of A-dmDT390-bisFv(UCHT1) intravenously twice daily for four consecutive days. Although transient elevation of liver transaminases in the high groups was observed, the A-dmDT390-bisFv(UCHT1) administration did not affect liver function, renal function, the hemogram, or produce serious organ histopathology. Adverse events included transient lethargy, inappetence and weight loss in high groups. A-dmDT390-bisFv(UCHT1) plasma half life was 26.95 min in rats and 18.33 min in squirrel monkeys. Immune responses to A-dmDT390-bisFv(UCHT1) were minimal in squirrel monkeys and mild in rats. In vitro cytokine release, T cell activation and CD3 epsilon receptor occupancy assays using human PBMC were further performed since rat and squirrel monkey T cells do not react with A-dmDT390-bisFv(UCHT1). A-dmDT390-bisFv(UCHT1) did not induce cytokine release or T cell activation. The A-dmDT390-bisFv(UCHT1) concentration for 50% CD3 epsilon receptor occupancy was 7.4 nM. The MTD of 200 microg/kg total provides a dose level sufficient for anti-tumor activity in vitro and in a rodent model. Therefore, we propose that this agent is a promising drug for patients with surface CD3+ T cell malignancies.

100 Deals associated with A-dmDT390-bisFv(National Institutes of Health)

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External Link

KEGG	Wiki	ATC	Drug Bank
-	A-dmDT390-bisFv(National Institutes of Health)	-	DB16307

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic melanoma	Phase 2	United States	University of Louisville	01 Feb 2014
Metastatic melanoma	Phase 2	United States	Angimmune LLC	01 Feb 2014
Cutaneous T-Cell Lymphoma	Phase 2	United States	Virogen Biotechnology, Inc.	-
Graft vs Host Disease	Phase 2	United States	Virogen Biotechnology, Inc.	-
Solid tumor	Phase 2	United States	Virogen Biotechnology, Inc.	-
Mycosis Fungoides	Discovery	United States	Angimmune LLC	01 Jan 2008
Sezary Syndrome	Discovery	United States	Angimmune LLC	01 Jan 2008
T-Cell Leukemia	Discovery	United States	Angimmune LLC	01 Jan 2008

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00611208 (Pubmed \| Haematologica) Manual	Phase 2	Cutaneous T-Cell Lymphoma	30	A-dmDT390-bisFv	(ktlbjeclni) = alofjefyzz pprjccegxd (hroasxejtw, 18 - 57) View more	Positive	01 Jun 2015
IND#100712 (ASCO2009)	Phase 1	Cutaneous T-Cell Lymphoma	6	A-dmDT390-bisFv(UCHT1)	(ffrwmexyzm) = bukspzbwgw couzxsolrq (plkilkqnxt ) View more	-	20 May 2009

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Translational Medicine

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Deal

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Core Patent

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Clinical Trial

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Approval

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Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

Regulation

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A-dmDT390-bisFv(National Institutes of Health)

Overview

Basic Info

Structure/Sequence

Related

External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Biosimilar

Regulation