RATIONALE: DTGM fusion protein may be able to locate cancer cells and stop them from growing.
PURPOSE: Phase I/II trial to study the effectiveness of DTGM fusion protein in treating patients who have recurrent or refractory acute myeloid leukemia.

Start Date01 Oct 2000

Sponsor / Collaborator

Wake Forest School of Medicine

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100 Clinical Results associated with DTGM fusion protein(NCI)

100 Translational Medicine associated with DTGM fusion protein(NCI)

100 Patents (Medical) associated with DTGM fusion protein(NCI)

Literatures (Medical) associated with DTGM fusion protein(NCI)

13 Feb 2019·Radiation ResearchQ3 · MEDICINE

dTMP-GH Fusion Protein Therapy Improves Survival after Radiation Injury Combined with Skin-Burn Trauma in Mice

Q3 · MEDICINE

Article

Author: Wan, Huimin ; Wang, Guojian ; Wang, Aiping ; Wang, Junping ; Wang, Song ; Su, Yongping ; Ran, Xinze ; Hao, Yuhui ; Xu, Yang ; Long, Shuang ; Wang, Tao ; Wang, Cheng ; Gao, Jining ; Li, Rong ; Zhao, Na ; Shen, Mingqiang

Exposure to ionizing radiation combined with traumatic tissue injury is an important life-threatening condition found in the civilian populations after nuclear and radiological events. The significance feature of radiation combined injury (RCI) is the severe combined effect, which makes the injury more complicated. At present, there are limited measures available to treat RCI. Here we show that a chimeric protein dTMP-GH, fusing human growth hormone (hGH) with a tandem dimer of thrombopoietin mimetic peptide (dTMP), could be an effective therapy agent for RCI in a mice model. In this study, using a RCI mouse model exposed to ⁶⁰Co γ-ray photons (6.0 Gy, 0.3 Gy/min) followed by a 20% total-body-surface-area burns (henceforth called: RB-CI) was established. Administration of dTMP-GH (200 ug/kg) for 10 consecutive days beginning at 24 h after injury improved survival rate during a 30-day observation period compared with the control vehicle group. dTMP-GH treatment also showed enhanced bone marrow hematopoiesis recovery determined by peripheral blood analysis and bone marrow histopathology. Meanwhile, dTMP-GH treatment accelerated skin wound closure and mitigated ileum injury in the RCI model. These results suggest that dTMP-GH may prove to be an effective therapeutic drug for RCI.

01 Dec 2014·Journal of the Renin-Angiotensin-Aldosterone SystemQ4 · MEDICINE

Constitutive activation of the renin-angiotensin system reduces visceral fat and improves glucose tolerance in mice

Q4 · MEDICINE

ArticleOA

Author: Van Obberghen, Emmanuel ; Lopez, Pascal ; Butori, Catherine ; Hofman, Paul ; Favre, Guillaume A ; Lebrun, Patricia ; Esnault, Vincent LM

Introduction: The renin-angiotensin system (RAS), and particularly angiotensin II, is involved in the control of energy balance, glucose homeostasis and kidney functions. The integrated impact of the RAS on glucose homeostasis is still a matter of debate. Materials and methods: We used a model of constitutive RAS activation in double transgenic mice (dTGM) carrying both human angiotensinogen and human renin genes. We evaluated energy balance, measured renal functions, performed glucose and insulin tolerance tests, and used ramipril to inhibit the angiotensin-converting enzyme. Results: dTGM had a lower physical activity and an increased food intake without change in body weight. Renal impairment was characterized by low-grade albuminuria. High urinary output secondary to polydipsia was associated with proximal tubule dysfunction. Compared to controls, dTGM had a lower hyperglycemia induced by an intraperitoneal glucose administration. This decrease was not due to changes in insulin sensitivity and/or secretion. dTGM had an increased creatinine production and a lower epididymal fat mass. Acute inhibition of angiotensin-converting enzyme with ramipril did not suppress this improved glucose tolerance profile. Conclusion: Chronic RAS activation is not sufficient to cause insulin resistance in mice. Moreover, adaptation to constitutive RAS activation in mice results in a better glucose tolerance.

01 Sep 2003·Clinical cancer research : an official journal of the American Association for Cancer Research

A phase II study of DT fusion protein denileukin diftitox in patients with fludarabine-refractory chronic lymphocytic leukemia.

Article

Author: Powell, Bayard L ; Black, Jennifer H ; Fleming, Donald R ; Gartenhaus, Ronald ; Leftwich, Carole ; Frankel, Arthur E ; Hall, Philip D

PURPOSEPatients with relapsed or refractory chronic lymphocytic leukemia (CLL) have a poor prognosis. We tested the safety and efficacy in these patients of a diphtheria fusion protein DAB(389)IL2 (denileukin diftitox) directed against the interleukin 2 receptor that is expressed by CLL cells.EXPERIMENTAL DESIGNDAB(389)IL2 was administered by 60 min i.v. infusions for 5 days every 21 days at 9 or 18 micro g/kg/day for up to eight cycles.RESULTSEighteen patients were treated. The mean age of the patients was 61.8 years. There were 14 males and 4 females. Two had Rai stage I, 6 had Rai stage II, and 10 had Rai stage IV. The mean number of prior treatments was 4.5 (range, 1-11). Responses were evaluated by peripheral CLL counts, computed tomography scans of all nodes and bone marrow biopsies. Twelve patients received greater than or equal to three cycles of DAB(389)IL2 and were evaluable for response. Eleven of 12 patients showed reductions of peripheral CLL cells, with 6 of 11 showing >/==" BORDER="0">95% reductions. Seven of 12 patients showed reductions of node diameters on exam and computed tomography scans, and 2 of 12 showed 60 and 80% shrinkage, respectively. Pre and postbone marrow biopsies showed a reduction in CLL marrow index in 11 patients. Seven of 11 patients had >50% reduction, including >/==" BORDER="0">98% reduction in 3 patients. DAB(389)IL2 produced 2 of 12 (17%) partial remission and 7 of 12 (58%) minimal responses. Progression-free intervals in the responders were 1, 1, 3+, 4, 9, 10, 10+, 14 and 19+ months. Toxicities were mild to moderate and included asymptomatic, transient transaminasemia, fever, asthenia, hypoalbuminemia, nausea, vomiting, myalgias, rash, anorexia, vascular leak syndrome, and elevated creatinine kinase. Antidiphtheria toxin antibody levels were variable and ranged from 0 to 9 micro g/ml (n = 5).CONCLUSIONSDAB(389)IL2 produced a rapid decrease of leukemic cells in the bone marrow and peripheral blood of most chemotherapy refractory CLL patients. Most patients also tolerated DAB(389)IL2 well, without significant myelosuppression and/or immunosuppression. The prolonged progression-free interval and subjectively observed quality-of-life in responders is intriguing. The results suggest DAB(389)IL2 has biological activity in patients with B-cell CLL. Follow-up studies of combinations or altered schedules or doses to improve the response rate are warranted.

100 Deals associated with DTGM fusion protein(NCI)

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Indication	Highest Phase	Country/Location	Organization	Date
Adult Acute Myeloblastic Leukemia	Phase 2	US	National Cancer Institute	31 Oct 2000
Refractory acute myeloid leukemia	Phase 2	US	National Cancer Institute	01 Oct 2000

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