Purine nucleoside phosphorylase inhibitors - an immunotherapy with novel mechanism of action for the treatment of melanoma
نویسنده
چکیده
Introduction Contrary to expectations based on the immuno-compromised clinical phenotype of the PNP-deficient patients, the present study demonstrates that PNP inhibitors (PNPi) can activate immune cells that can help mount a robust antitumor response. PNP deficiency in humans lead to elevation of plasma guanosine [1]. In the present study, we demonstrate that guanosine can activate toll like receptor 2 (TLR2) and TLR4. Powerful immune-stimulatory properties of TLR2 and TLR4 agonist have been exploited for their potential as anti-cancer agents and as an adjuvant in cancer vaccines.
منابع مشابه
Expression of human malaria parasite purine nucleoside phosphorylase in host enzyme-deficient erythrocyte culture. Enzyme characterization and identification of novel inhibitors.
The intraerythrocytic human malaria parasite, Plasmodium falciparum, requires a source of hypoxanthine for nucleic acid synthesis and energy metabolism. Adenosine has been implicated as a major source for intraerythrocytic hypoxanthine production via deamination and phosphorolysis, utilizing adenosine deaminase and purine nucleoside phosphorylase, respectively. To study the expression and chara...
متن کاملOne-third-the-sites transition-state inhibitors for purine nucleoside phosphorylase.
Genetic defects in human purine nucleoside phosphorylase cause T-cell deficiency as the major phenotype. It has been proposed that efficient inhibitors of the enzyme might intervene in disorders of T-cell function. Compounds with features of the transition-state structure of purine nucleoside phosphorylase were synthesized and tested as inhibitors. The transition-state structure for purine nucl...
متن کاملBystander Killing of Melanoma Cells Using the Human Tyrosinase Promoter to Express the Escherichia coli Purine Nucleoside Phosphorylase Gene1
We used a gene transfer-based system to generate highly toxic purine bases in tumor cells transfected with the Escherichia coli purine nucleoside phosphorylase (PNP) gene. Because these toxic purines are mem brane permeant, they mediate effective killing of neighboring cells that do not express E. coli PNP ("bystander" toxicity). In mixed cultures contain ing increasing percentages of cells wit...
متن کاملNucleoside Phosphorylase Gene Purine Escherichia coli Tyrosinase Promoter to Express the Bystander Killing of Melanoma Cells Using the Human
We used a gene transfer-based system to generate highly toxic purine bases in tumor cells transfected with the Escherichia coli purine nucleoside phosphorylase (PNP) gene. Because these toxic purines are mem brane permeant, they mediate effective killing of neighboring cells that do not express E. coli PNP ("bystander" toxicity). In mixed cultures contain ing increasing percentages of cells wit...
متن کاملFacile synthesis of 9-substituted 9-deazapurines as potential purine nucleoside phosphorylase inhibitors.
A facile synthesis of 9-substituted 9-deazapurines as potential inhibitors of purine nucleoside phosphorylase has been achieved by the direct Friedel-Crafts aroylation or arylmethylation of 9-deazapurines using trifluoromethanesulfonic acid as catalyst. The aroylated 9-deazapurines could be transformed into the corresponding 9-aryimethyl derivatives by the Wolff-Kishner reaction. A novel synthe...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 3 شماره
صفحات -
تاریخ انتشار 2015