Cell lines

Cultured mononuclear cells and purified γδ+ tumour cells from bone marrow or peripheral blood of four patients with hepatosplenic γδ+ T-cell lymphoma

Preparation method

The solubility of this compound in DMSO is >13.4 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

10-100 μM, 48 h

Applications

Pentostatin (10 μM) displayed an early and selective cytotoxic effect on γδ+ tumour T cells. After 48 h of in vitro exposure to pentostatin reduced the absolute number of viable CD3+/γδ+ tumour T cells. Exposure to pentostatin (5 days) plus dAdo revealed the persistence of normal CD3+/αβ+ T cells. Combination of pentostatin (10–100 μM) plus dAdo dose-dependently inhibited clonogenic growth and [3H]-thymidine incorporation in purified CD3+/CD4-/CD8-γδ+ tumour cells.

Animal models

Mice infected with Trypanosoma evansi

Dosage form

2 mg/kg

Application

Pentostatin (2 mg/kg) in combination with cordycepin (2 mg/kg) was 100% effective in the T. evansi-infected mice. There was an increase in levels of some biochemical parameters, especially on liver enzymes, which were accompanied by histological lesions in the liver and kidneys. Pentostatin individually showed no curative effect on infected groups

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Pentostatin is a nucleoside analog and also is a potent inhibitor of adenosine deaminase. It has a broad spectrum of immunomodulatory activities. [1] The capacity of this purine analogue to inhibit proliferation and to induce apoptosis of T-cells in combination with its mild toxicity results in the approach to use pentostatin in steroid-refractory aGvHD.[2]
Chronic graft-versus-host disease (GVHD) is the main cause of late morbidity and non–relapse mortality after hematopoietic stem cell transplantation (HSCT).
Most relevant to GVHD, Pentostatin causes marked reduction of CD4 and CD8 cells. There is also significant B-cell depletion with reduction of IgG levels.13 This should allow it to affect GVHD at the cellular level and thus has the potential to address the many manifestations of chronic GVHD. Pentostatin is found to be active in a phase 1 study in refractory acute GVHD. A phase 2 study of pentostatin in heavily pretreated patients (median age, 33 years; median of 4 prior regimens) with chronic GVHD showed a 55% objective response rate in 58 patients.
In comparison with other treatment options, pentostatin has some favourable characteristics and its effect is sustainable and the majority of responding patients survived. The costs for pentostatin are relatively low and the toxicity is moderate.
References:
[1]David A. Jacobsohn, Andrew L. Gilman, Alfred Rademaker et al. Evaluation of pentostatin in corticosteroid-refractory chronic graft-versus-host disease in children: a Pediatric Blood and Marrow Transplant Consortium study. BLOOD, 12 NOVEMBER 2009 _ VOLUME 114, NUMBER 20
[2] Stefan A. Klein1, Gesine Bug2, Sabine Mousset2 et al. Long term outcome of patients with steroid-refractory acute intestinal graft versus host disease after treatment with pentostatin. British Journal of Haematology, 154, 141–155