PNP Therapeutics

The PNP Technology

Publications by PNP Therapeutics

Rosenthal EL, Chung TK, Parker WB, Allan PW, Clemons L, Lowman D, Hong J, Hunt FR, Richman J, Conry RM, Mannion K, Carroll WR, Nabell L, Sorscher EJ (2015) Phase 1 dose-escalating trial of Escherichia coli purine nucleoside phosphorylase and fludarabine gene therapy for advanced solid tumors. Annals of Oncology 26: 1481-1487.

Sorscher EJ, Hong JS, Allan PW, Waud WR, Parker WB (2012) In vivo antitumor activity of intratumoral fludarabine phosphate in refractory tumors expressing E. coli purine nucleoside phosphorylase. Cancer Chemotherapy and Pharmacology 70: 321-329.

Hassan AEA, Abou-Elkhair RAI, Riordan JM, Allan PW, Parker WB, Khare R, Waud WR, Montgomery JA, Secrist JA III (2012) Synthesis and evaluation of the substrate activity of C-6 substituted purine ribosides with E. coli purine nucleoside phosphorylase: Palladium mediated cross-coupling of organozinc halides with 6-chloropurine nucleosides. Eur. J. Med. Chem. 47: 167-174.

Parker WB, Allan PW, Waud WR, Hong JS, Sorscher EJ (2011) Effect of expression of adenine phosphoribosyltransferase on the in vivo anti-tumor activity of prodrugs activated by E. coli purine nucleoside phosphorylase. Cancer Gene Therapy 18: 390-398. PMC3096718

Tai CK, Wang W, Lai YH, Logg CR, Parker WB, Li YF, Hong JS, Sorscher EJ, Chen TC, Kasahara N (2010) Enhanced efficiency of prodrug activation therapy by tumor-selectively replicating retrovirus vectors armed with the Escherichia coli purine nucleoside phosphorylase. Cancer Gene Therapy 17: 614-623. PMC2938767

Hassan AEA, Parker WB, Allan PW, Secrist JA III (2009) Regioselective metalation of 6-methylpurines: synthesis of fluoromethyl purines and related nucleosides for suicide gene therapy of cancer. Nucleosides, Nucleotides and Nucleic Acids 28: 642-656.

Zhang Y, Parker WB, Sorscher EJ, Ealick SE (2005) PNP anticancer gene therapy. Current Topics in Medicinal Chemistry 5: 1259-1274.

Parker WB, Allan PW, Ealick SE, Sorscher EJ, Hassan AEA, Silamkoti AV, Fowler AT, Waud WR, Secrist JA III (2005) Design and evaluation of 5’-modified nucleoside analogs as prodrugs for an E. coli purine nucleoside phosphorylase mutant. Nucleosides, Nucleotides, and Nucleic Acids 24: 387-392.

Silamkoti AV, Allan PW, Hassan AE, Fowler AT, Sorscher EJ, Parker WB, Secrist JA 3rd (2005) Synthesis and biological activity of 2-fluoro adenine and 6-methyl purine nucleoside analogs as prodrugs for suicide gene therapy of cancer. Nucleosides, Nucleotides, and Nucleic Acids 24: 881-885.

Bharara S, Sorscher EJ, Gillespie GY, Lindsey JR, Hong JS, Curlee KV, Allan PW, Gadi VK, Alexander SA, Secrist JA 3rd, Parker WB, Waud WR (2005) Antibiotic-mediated chemoprotection enhances adaptation of E. coli PNP for herpes simplex virus-based glioma therapy. Hum Gene Ther. 16: 339-47.

Hong JS, Waud WR, Levasseur DN, Townes TM, Wen H, McPherson SA, Moore BA, Bebok Z, Allan PW, Secrist JA 3rd, Parker WB, and Sorscher EJ (2004) Excellent In vivo Bystander Activity of Fludarabine Phosphate against Human Glioma Xenografts that Express the Escherichia coli Purine Nucleoside Phosphorylase Gene. Cancer Res. 64: 6610-6615.

Curlee KV, Parker WB, and Sorscher EJ (2004) Tumor sensitization to purine analogs by E. coli PNP. Methods Mol. Med. 90: 223-246.

Bennett EM, Anand R, Allan PW, Hassan AE, Hong JS, Levasseur DN, McPherson DT, Parker WB, Secrist JA 3rd, Sorscher EJ, Townes TM, Waud WR, and Ealick SE (2003) Designer gene therapy using an Escherichia coli purine nucleoside phosphorylase/prodrug system. Chem. Biol. 10: 1173-1181.

Hassan AE, Parker WB, Allan PW, Montgomery JA, and Secrist JA 3rd. (2003) Selective metalation of 6-methylpurines: synthesis of 6-fluoromethylpurines and related nucleosides. Nucleosides Nucleotides Nucleic Acids 22: 747-749.

Bennett EM, Li C, Allan PW, Parker WB, and Ealick SE (2003) Structural basis for substrate specificity of Escherichia coli purine nucleoside phosphorylase. J. Biol. Chem. 278: 47110-47118.

Gadi VK, Alexander SD, Waud WR, Allan PW, Parker WB, and Sorscher EJ (2003) A long-acting suicide gene toxin, 6-methylpurine, inhibits slow growing tumors after a single administration. J. Pharmacol. Exp. Ther. 304: 1280-1284.

Parker WB, Allan PW, Hassan AEA, Secrist JA III, Sorscher EJ, and Waud WR (2003) Antitumor activity of 2-fluoro-2'-deoxyadenosine against tumors that express Escherichia coli purine nucleoside phosphorylase. Cancer Gene Therapy 10: 23-29.

Hassan AEA, Shortnacy-Fowler AT, Montgomery JA, and Secrist JA III (2000) A convenient synthesis of 2'-deoxy-2-fluoroadenosine; a potential prodrug for suicide gene therapy. Nucleosides, Nucleotides, and Nucleic Acids 19: 559-565.

Gadi VK, Alexander SD, Kudlow JE, Allan P, Parker WB, and Sorscher EJ (2000) In vivo sensitization of ovarian tumors to chemotherapy by expression of E. coli purine nucleoside phosphorylase in a small fraction of tumor cells. Gene Therapy 7: 1738-1743.

Hassan AE, Abou-Elkair RA, Montgomery JA, and Secrist JA III (2000) Convenient syntheses of 6-methylpurine and related nucleosides. Nucleosides, Nucleotides, and Nucleic Acids 19:1123-1134.

Secrist JA III, Parker WB, Allan PW, Bennett LL Jr, Waud WR, Truss JW, Fowler AT, Montgomery JA, Ealick SE, Wells AH, Gillespie GY, Gadi VK, and Sorscher EJ (1999). Gene therapy of cancer: Activation of nucleoside prodrugs with E. coli purine nucleoside phosphorylase. Nucleosides Nucleotides 18: 745-757.

Parker WB, Allan PW, Shaddix SC, Rose LM, Speegle HF, Gillespie GY, and Bennett LL Jr (1998) Metabolism and metabolic actions of 6-methylpurine and 2-fluoroadenine in human cells. Biochem. Pharmacol. 55: 1673-1681.

Hughes BW, King SA, Allan PW, Parker WB, and Sorscher EJ (1998) Cell to cell contact is not required for bystander cell killing by E. coli purine nucleoside phosphorylase. J. Biol. Chem. 273: 2322-2328.

Parker WB, King SA, Allan PW, Bennett LL Jr, Secrist JA III, Montgomery JA, Gilbert KS, Waud WR, Wells AH, Gillespie GY, and Sorscher EJ (1997) In vivo gene therapy of cancer with E. coli purine nucleoside phosphorylase. Human Gene Therapy 8: 1637-1644.

Hughes BW, Wells AH, Bebok Z, Gadi VK, Garver RI Jr, Parker WB, and Sorscher EJ (1995) Bystander killing of melanoma cells using the human tyrosinase promoter to express the Escherichia coli purine nucleoside phosphorylase gene. Cancer Res. 55: 3339-3345.

Sorscher EJ, Peng S, Bebok Z, Allan PW, Bennett LL Jr, and Parker WB (1994) Tumor cell bystander killing in colonic carcinoma utilizing the E. coli Deo D gene to generate toxic purines. Gene Therapy 1: 233-238.

E. coli PNP Publications by Other Laboratories

Cacciapuoti G, Bagarolo ML, Martino E, Scafuri B, Marabotti A, Porcelli M (2015) Efficient Fludarabine-Activating PNP From Archaea as a Guidance for Redesign the Active Site of E. Coli PNP. J Cell Biochem. [Epub ahead of print]

Lai Y-H, Lin C-C, Chen S-H, Tai C-K (2015) Tumor-specific suicide gene therapy for hepatocellular carcinoma by transcriptionally targeted retroviral replicating vectors. Gene Therapy 22: 155-162.

Guillen K, Kurkjian C, Harrison R (2014) Targeted enzyme prodrug therapy for metastatic prostate cancer – A comparative study of L-methionase, purine nucleoside phosphorylase, and cytosine deaminase. Journal of Biomedical Science 21: 65.

Krais JJ, De Crescenzo O, Harrison RG (2013) Purine nucleoside phosphorylase targeted by annexin v to breast cancer vasculature for enzyme prodrug therapy. PLoS One. 2013 Oct 3;8(10):e76403.

Chen ZH, Huang GL, Tu YQ, Jiang Y, Dai WX (2013) Dual specific antitumor effects of Semliki Forest virus-based DNA vector carrying suicide Escherichia coli purine nucleoside phosphorylase gene via Salmonella. Int J Oncol. Apr 16. doi: 10.3892/ijo.2013.1900. [Epub ahead of print]

Chen G, Tang B, Yang BY, Chen JX, Zhou JH, Li JH, Hua ZC (2012) Tumor-targeting Salmonella typhimurium, a natural tool for activation of prodrug 6MePdR and their combination therapy in murine melanoma model. Appl Microbiol Biotechnol. 2012 Aug 7. [Epub ahead of print]

Xie X, Guo J, Kong Y, Xie GX, Li L, Lv N, Xiao X, Tang J, Wang X, Liu P, Yang M, Xie Z, Wei W, Xie X (2011) Targeted expression of E. coli purine nucleoside phosphorylase and Fludara for prostate cancer therapy. J Gene Med. 13: 680-691.

Singh PP, Joshi S, Russell PJ, Nair S, Khatri A (2011) Purine Nucleoside Phosphorylase mediated molecular chemotherapy and conventional chemotherapy: a tangible union against chemoresistant cancer. BMC Cancer. 11: 368.

Bossow S, Grossardt C, Temme A, Leber MF, Sawall S, Rieber EP, Cattaneo R, von Kalle C, Ungerechts G (2011) Armed and targeted measles virus for chemovirotherapy of pancreatic cancer. Cancer Gene Therapy 18: 598-608.

Singh PP, Joshi S, Russell PJ, Verma ND, Wang X, Khatri A (2011) Molecular chemotherapy and chemotherapy: a new front against late-stage hormone-refractory prostate cancer. Clin Cancer Res. 17: 4006-4018.

Hébrard C, Dumontet C, Jordheim LP (2009) Development of gene therapy in association with clinically used cytotoxic deoxynucleoside analogues. Cancer Gene Ther. 16: 541-550.

Afshar S, Olafsen T, Wu AM, Morrison SL (2009) Characterization of an engineered human purine nucleoside phosphorylase fused to an anti-her2/neu single chain Fv for use in ADEPT. J Exp Clin Cancer Res. 28: 147-.

Afshar S, Sawaya MR, Morrison SL (2009) Structure of a mutant human purine nucleoside phosphorylase with the prodrug, 2-fluoro-2'-deoxyadenosine and the cytotoxic drug, 2-fluoroadenine. Protein Sci. 18: 1107-1114.

Afshar S, Asai T, Morrison SL (2009) Humanized ADEPT comprised of an engineered human purine nucleoside phosphorylase and a tumor targeting peptide for treatment of cancer. Mol Cancer Ther. 8: 185-193.

Stritzker J, Pilgrim S, Szalay AA, Goebel W. Prodrug converting enzyme gene delivery by L. monocytogenes (2008) BMC Cancer. 8: 94-103.

Fu W, Lan H, Li S, Han X, Gao T, Ren D (2008) Synergistic antitumor efficacy of suicide/ePNP gene and 6-methylpurine 2'-deoxyriboside via Salmonella against murine tumors. Cancer Gene Ther. 15: 474-484.

Fu W, Lan H, Liang S, Gao T, Ren D (2008) Suicide gene/prodrug therapy using salmonella-mediated delivery of Escherichia coli purine nucleoside phosphorylase gene and 6-methoxypurine 2-deoxyriboside in murine mammary carcinoma 4T1 model. Cancer Sci. 99: 1172-1179

Cai X, Zhou J, Chang Y, Sun X, Li P, Lin J (2008) Targeting gene therapy for hepatocarcinoma cells with the E. coli purine nucleoside phosphorylase suicide gene system directed by a chimeric alpha-fetoprotein promoter. Cancer Lett. 264: 71-82.

Ungerechts G, Springfield C., Frenzke ME, Lampe J, Johnston P, Parker WB, Sorscher EJ, Cattaneo R (2007) Lymphoma chemovirotherapy: CD20-targeted and convertase-armed measles virus can synergize with fludarabine. Cancer Res. 67: 10939-10947.

Ungerechts G, Springfield C., Frenzke ME, Lampe J, Parker WB, Sorscher EJ, Cattaneo R (2007) An immunocompetent murine model for oncolysis with an armed and targeted measles virus. Molecular Therapy 15: 1991-1997.

Zhou JH, Tang B, Liu XL, He DW, Yang DT (2007) hTERT-targeted E. coli purine nucleoside phosphorylase gene/6-methylpurine deoxyribose therapy for pancreatic cancer. Chin Med J Aug 120: 1348-1352.

Deharvengt S, Rejiba S, Wack S, Aprahamian M, Hajri A (2007) Efficient electrogene therapy for pancreatic adenocarcinoma treatment using the bacterial purine nucleoside phosphorylase suicide gene with fludarabine. Int J Oncol. 30: 1397-1406.

Both GW, Cameron F, Collins A, Lockett LJ, Shaw J. (2007) Production and release testing of ovine atadenovirus vectors. Methods Mol Med. 130: 69-90.

Kikuchi E, Menendez S, Ozu C, Ohori M, Cordon-Cardo C, Logg CR, Kasahara N, Bochner BH (2007) Delivery of replication-competent retrovirus expressing Escherichia coli purine nucleoside phosphorylase increases the metabolism of the prodrug, fludarabine phosphate and suppresses the growth of bladder tumor xenografts. Cancer Gene Ther. 2007 14: 279-86.

Cai XK, Zhou JL, Zhou HJ, Zhang L, Wu JH, Lin JS (2006) Killing effect of PNP/MeP-dR suicide gene system driven by an AFP promoter AF0.3 on AFP-positive hepatoma cells. Ai Zheng. 25: 1334-1339.

Cai X, Zhou J, Lin J, Sun X, Xue X, Li C. (2005) Experimental studies on PNP suicide gene therapy of hepatoma. J Huazhong. Univ Sci Technolog Med Sci. 25:178-181.

Arvidsson Y, Sumantran V, Watt F, Uramoto H, Funa K. (2005) Neuroblastoma-specific cytotoxicity mediated by the Mash1-promoter and E. coli purine nucleoside phosphorylase. Pediatr Blood Cancer. 44: 77-84.

Heinkelein M, Hoffmann U, Lucke M, Imrich H, Muller JG, Meixensberger J, Westphahl M, Kretschmer A, Rethwilm A. (2005) Experimental therapy of allogeneic solid tumors induced in athymic mice with suicide gene-transducing replication-competent foamy virus vectors. Cancer Gene Ther. 12: 947-953

Asai T, Wims LA, Morrison SL. (2005) An interaction between S*tag and S*protein derived from human ribonuclease 1 allows site-specific conjugation of an enzyme to an antibody for targeted drug delivery. J Immunol Methods. 299: 63-76.

Asai T, Trinh R, Ng PP, Penichet ML, Wims LA, Morrison SL. (2005) A human biotin acceptor domain allows site-specific conjugation of an enzyme to an antibody-avidin fusion protein for targeted drug delivery. Biomol Eng. 21: 145-155.

Deharvengt S, Wack S, Aprahamian M, Hajri A. (2005) Transcriptional tumor-selective promoter targeting of E. coli purine nucleoside phosphorylase for pancreatic cancer suicide gene therapy. J Gene Med. 7: 672-680.

Martiniello-Wilks R, Wang XY, Voeks DJ, Dane A, Shaw JM, Mortensen E, Both GW, and Russell PJ (2004) Purine nucleoside phosphorylase and fludarabine phosphate gene-directed enzyme prodrug therapy suppresses primary tumour growth and pseudo-metastases in a mouse model of prostate cancer. J Gene Med. 6: 1343-1357.

Wang XY, Martiniello-Wilks R, Shaw JM, Ho T, Coulston N, Cooke-Yarborough C, Molloy PL, Cameron F, Moghaddam M, Lockett TJ, Webster LK, Smith IK, Both GW, and Russell PJ (2004) Preclinical evaluation of a prostate-targeted gene-directed enzyme prodrug therapy delivered by ovine atadenovirus. Gene Therapy 11: 1559-1567.

Critchley RJ, Jezzard S, Radford KJ, Goussard S, Lemoine NR, Grillot-Courvalin C, Vassaux G (2004) Potential therapeutic applications of recombinant, invasive E. coli. Gene Therapy 11: 1224-1233

Deharvengt S, Wack S, Uhring M, Aprahamian M, and Hajri A (2004) Suicide gene/prodrug therapy for pancreatic adenocarcinoma by E. coli purine nucleoside phosphorylase and 6-methylpurine 2'-deoxyriboside. Pancreas 28: E54-64.

Martiniello-Wilks R, Dane A, Voeks DJ, Jeyakumar G, Mortensen E, Shaw JM, Wang XY, Both GW, and Russell PJ (2004) Gene-directed enzyme prodrug therapy for prostate cancer in a mouse model that imitates the development of human disease. J. Gene Med. 6: 43-54.

Messina M, Yu DM, Both GW, Molloy PL, Robinson BG (2003) Calcitonin-specific transcription and splicing targets gene-directed enzyme prodrug therapy to medullary thyroid carcinoma cells. J Clin Endocrinol Metab 88: 1310-1318.

Voeks D, Martiniello-Wilks R, Madden V, Smith K, Bennetts E, Both GW, and Russell PJ (2002) Gene therapy for prostate cancer delivered by ovine adenovirus and mediated by purine nucleoside phosphorylase and fludarabine in mouse models. Gene Therapy 9: 759-768.

Martiniello-Wilks R, Tsatralis T, Russell P, Brookes DE, Zandvliet D, Lockett LJ, Both GW, Molloy PL, and Russell PJ (2002) Transcription-targeted gene therapy for androgen-independent prostate cancer. Cancer Gene Therapy 9: 443-452.

Krohne TU, Shankara S, Geissler M, Roberts BL, Wands JR, Blum HE, and Mohr L (2001) Mechanisms of cell death induced by suicide genes encoding purine nucleoside phosphorylase and thymidine kinase in human hepatocellular carcinoma cells in vitro. Hepatology 34: 511-518.

Bzowska A, Kulikowska E, and Shugar D (2000) Purine nucleoside phosphorylases: properties, functions, and clinical aspects. Pharmacol. Ther. 88: 349-425.

Mohr L, Shankara S, Yoon SK, Krohne TU, Geissler M, Roberts B, Blum HE, and Wands JR (2000) Gene therapy of hepatocellular carcinoma in vitro and in vivo in nude mice by adenoviral transfer of the Escherichia coli purine nucleoside phosphorylase gene. Hepatology 31: 606-614.

Both GW (2000) Nucleic Acid delivery with ovine adenoviral vectors. US patent number 6,020,172.

Park BJ, Brown CK, Hu Y, Alexander HR, Horti J, Raje S, Figg WD, and Bartlett DL (1999) Augmentation of melanoma-specific gene expression using a tandem melanocyte-specific enhancer results in increased cytotoxicity of the purine nucleoside phosphorylase gene in melanoma. Human Gene Therapy 10: 889-898.

Puhlmann M, Gnant M, Brown CK, Alexander HR, and Bartlett DL (1999) Thymidine kinase-deleted vaccinia virus expressing purine nucleoside phosphorylase as a vector for tumor-directed gene therapy. Human Gene Therapy 10: 649-657.

Martiniello-Wilks R, Garcia-Aragon J, Daja MM, Russell P, Both GW, Molloy PL, Lockett LJ, and Russell PJ (1998) In vivo gene therapy for prostate cancer: Preclinical evaluation of two different enzyme-directed prodrug therapy systems delivered by identical adenovirus vectors. Human Gene Therapy 9: 1617-1626.

Both GW (1997) Gene Therapy using ovine adenoviral vectors. International publication number WO 97/06826.

Lockett L J, Molloy PL, Russell PJ, and Both GW (1997) Relative efficiency of tumor cell killing in vitro by two enzyme-prodrug systems delivered by identical adenovirus vectors. Clin. Cancer. Res. 3: 2075-2080.

Nestler U, Heinkelein M, Lucke M, Meixensberger J, Scheurlen W, Kretschmer A, and Rethwilm A (1997) Foamy virus vectors for suicide gene therapy. Gene Therapy 4: 1270-1277.

Fathi R, Nawoschik KJ, Zavoda M, and Cook AF (1997) Enzymatic synthesis of 2'5'-dideoxy purine nucleosides and related compounds. Nucleosides and Nucleotides 16: 1907-1920.

Da Costa LT, Jen J, He TC, Chan TA, Kinzler KW, and Vogelstein B (1996) Converting cancer genes into killer genes. Proc. Natl. Acad. Sci. USA 93: 4192-4196.

Anderson-McKay JE, Both GW, and Simpson GW (1996) Stereoselective synthesis of 6-methyl-9-(2-deoxy-Β-D-erythro-pentofuranosyl)purine. Nucleosides and Nucleotides 15: 1307-1313.