Advanced search
Publication Cover
Emerging Drugs Volume 6, 2001 - Issue 1
Journal homepage
26
Views
2
CrossRef citations to date
0
Altmetric
Review

Clinical trials of a new class of therapeutic agents: antisense oligonucleotides

Umberto Galderisi Dipartimento di Medicina Sperimentale, Via Costantinopoli 16, 80138 Napoli, Italy. [email protected]
,
M Cipollaro Dipartimento di Medicina Sperimentale, Via Costantinopoli 16, 80138 Napoli, Italy. [email protected]
&
A Cascino Dipartimento di Medicina Sperimentale, Via Costantinopoli 16, 80138 Napoli, Italy. [email protected]
Pages 69-79 | Published online: 24 Feb 2005

Bibliography

  • AGRAWAL S, IYER RP: Modified oligonucleotides as therapeutic and diagnostic agents. CUIT. Opin. Biotechnol (1995) 6:12–19.
  • •Examples of modified ODNs.
  • GALDERISI U, CASCINO A, GIORDANO A: Antisense oligonucleotides as therapeutics agents. J. Cell. Physiol (1999) 181:251–257.
  • •Several examples of clinical trials with antisense ODNs.
  • WAGNER RW: The state of art in antisense research. Nature Med. (1995) 1:1116–1118.
  • WAGNER RW, FLANAGAN WM: Antisense technology and prospects for therapy of viral infections and cancer. Mol. Med. Today (1997) 3:31–38.
  • •Deals with antisense open problems in clinical trials.
  • AGRAWAL S: Antisense oligonucleotides: towards clinical trial. Trends Biotechnol (1996) 14:376–387.
  • •Problems and solutions for antisense clinical trials.
  • BRADBURY J: Antisense drugs move towards the clinic. Lancet (1997) 349:259.
  • CROOKE ST, BENNET CF: Progress in antisense oligonu-cleotide therapeutics. Ann. Rev. Pharmacol. Toxicol (1996) 36:107–129.
  • GALDERISI U, DI BERNARDO G, MELONE MAB, et al.: Antisense inhibitory effects: a comparison between 3'-partial and full phosphorothioate antisense oligonucleotides. J. Cell. Biochem. (1999) 74:31–37.
  • STEIN CA: Does antisense exist Nature Med. (1995) 1:119–121.
  • LAITINEN M, YLA-HERTTUALA S: Vascular gene transferfor the treatment of restenosis and atherosclerosis. Curr. Opin. Lipidol (1998) 9:465–469.
  • MANNION JD, ORMONT ML, SHI Y, et al.: Saphenous veingraft protection: effects of c-myc antisense. j Thorac. Cardiovasc. Surg. (1998) 115:152–161.
  • IVERSEN PL, COPPLE BL, TEWARY HK: Pharmacology and toxicology of phosphorothioate oligonucleotides in the mouse, rat, monkey and man. Toxkol. Lett. (1995) 82/83:425–430.
  • LEEDS JM, HENRY SP, BISTNER S, SCHERRILL S, WILLIAMS K, LEVIN AA: Pharmacokinetics of an antisense oligonucleotide injected intravitreally in monkeys. Drug Metab. Dispos. (1998) 26:670–675.
  • •One of the few studies on monkeys.
  • LOKE SL, STEIN CA, ZHANG XH, et al.: Characterization of oligonucleotide transport into living cells. Proc. Natl. Acad. Sci. USA (1989) 86:3474–3478.
  • AGRAWAL S, TENSAMANI J, GALBRAITH W, TANG J: Pharmacokinetics of antisense nucleotides. Clin. Pharmacokinet. (1995) 28:7–16.
  • BELTINGER C, SARAGOVI HU, SMITH RM, et al: Binding, uptake and intracellular trafficking of phosphorothioate-modified oligodeoxynucleotides. Clin. Invest. (1995) 95:1814–1823.
  • ••In-depth studies on ODN uptake.
  • LEDLEY TS, LEDLEY FD: Multicompartment, numerical model of cellular events in the pharmacokinetics of gene therapy. Hum. Gene Ther. (1994) 5:679–691.
  • COSSUM PA, SASMOR H, DELLINGER D: Pharmacoki-netics of a 14C-labeled phosphorothioate oligonucleo-tide ISIS2105 after intra-venous administration to rats. Pharmacol Exp. Ther. (1993) 267:1181–1190.
  • GALBRAITH WM, HOBSON WC, GICLAS PC, SCHEEHTER PI, AGRAWAL S: Complement activation and hemody-namic changes following intravenous administration of phosphorothioate oligonucleotides in the monkey. Antisense Res. Dev. (1994) 4:201–206.
  • •Side effects of antisense therapy.
  • IVERSEN PL, ZHU S, MEYER A, ZON G: Cellular uptake and sub-cellular distribution of phosphorothioate oligonucleotides into cultured cells. Antisense Res. Dev. (1992) 2:211–222.
  • RAYNAUD Fl, ORR RM, GODDARD PM, et al: Pharma-cokinetics of G3139, a phosphorothioate oligode-oxynucleotide antisense to Bc1-2, after intravenous administration or continuous subcutaneous infusion to mice. J. Pharmacol. Exp. Ther. (1997) 281:420–427.
  • ZHANG R, DIASIO RB, LU Z, et al: Pharmacokinetics and tissue disposition in rats of an oligodeoxynucleotide phosphorothioate (GEM91) developed as a therapeutic agent for human immunodeficiency virus Type 1. Biochem. Pharmacol (1995) 49:929–939.
  • ZHANG R., LU Z, ZHANG X, DIASIO RB, et al.: In vivo stability, disposition and metabolism of a 'hybrid' oligonucleotide phosphorothioate in rats. Biochem. Pharmacol (1995) 50:545–556.
  • STEIN CA, CHENG YC: Antisense oligonucleotides as therapeutic agents- is the bullet really magical Science (1993) 261:1004–1012.
  • GEARY RS, LEEDS JM, FITCHETT J, et al: Pharmacoki-netics and metabolism in mice of a phosphorothioate oligonucleotide antisense inhibitor of C-raf-1 kinase expression. Drug Metab. Dispos. (1997) 25:1272–1281.
  • JUNKER U, BAKER J, KALFOGLOU CS, VERES G, KANESHIMA H, BOHNLEIN E: Antiviral potency of drug-gene therapy combinations against human immunodeficiency virus Type 1. AIDS Res. Hum. RetrovE ruses (1997) 13:1395–1402.
  • SHI Y, FARD A, GALEO A, et al: Transcatheter delivery ofc-myc antisense oligomers reduces neointimal formation in a porcine model of coronary artery balloon injury. Circulation (1994) 90:944–951.
  • NESBIT CE, TERSAK JM, PROCHOWNIK EV: MYC oncogenes and human neoplastic disease. Oncogene (1999) 18:3004–3016.
  • CASELMANN WH, EISENHARDT S, ALT M: Synthetic antisense oligodeoxynucleotidesas potential drugs against hepatitis C. Intervirology (1997) 40:394–399.
  • LIMA WF, BROWN-DRIVER V, FOX M, HANECAK R and BRUICE TVV: Combinatorial screening and rational optimization for hybridization to folded hepatitis C virus RNA of oligonucleotides with biological antisense activity. J. Biol. Chem. (1997) 272:626–638.
  • GOKHALE PC, SOLDATENKOV V, WANG FH, RAHMAN A,DRITSCHILO A, KASID U: Antisense raf oligodeoxyribo-nucleotide is protected by liposomal encapsulation and inhibits Raf-1 protein expression in vitro and in viva implication for gene therapy of radio-resistant cancer. Gene Ther. (1997) 12:1289–1299.
  • BAYEVER E, IVERSEN PL, BISHOP MR, et al.: Systemicadministration of a phosphorothioate oligonucleotide with a sequence complementary to p53 for acute myelo gen ous leukemia and myelodysplastic syndrome: initial results of a Phase I trial. Antisense Res. Dev. (1993) 3:383–390.
  • BAYEVER E, HAINES.M, IVERSEN PL, et al.: Selectivecytotoxicity to human leukemic myeloblasts produced by oligodeoxyribonucleotide phosphorothioates complementary to p53 nucleotide sequences. Leuk. Lymphoma (1994) 12:223–231.
  • BISHOP MR, IVERSEN PL, BAYEVER E, et al.: Phase I trial of an antisense oligonucleotide OL(1)p53 in hematologic malignancies. J. Clin. Oncol. (1996) 14:1320–1326.
  • YUEN A, HALSEY J, FISHER GA, et al.: Phase I study of an antisense oligonucleotide to protein kinase C-a (ISIS 3521 /CGP 64128A) in patients with cancer. Clin. Cancer Res. (1999) 5:3357–3363.
  • CALABRETTA B, SKORSKI T, RATAJCZAK MZ, GEWIRTZAM: Antisense strategies in the treatment of leukemias. Semin. Oncol (1996) 23:78–87.
  • CHAUDHARY KS, ABEL PD, LALANI EN: Role of the Bc1-2gene family in prostate cancer progression and its implications for therapeutic intervention. Environ. Health. Perspect. (1999) 107 (Suppl. 1) :49–57. Relationship between Bc1-2 gene and prostate cancer.
  • GEWIRTZ AM: Potential therapeutic applications ofantisense oligodeoxynucleotides in the treatment of chronic myelogeneous leukemia. Leuk. Lymphoma (1993) 11:131–137.
  • REED JC: Regulation of apoptosis by Bc1-2 familyproteins and its role in cancer and chemoresistance. Curr. Opin. Oncol. (1995) 7:541–546.
  • REED JC, STEIN C, SUBASINGHE C, et al.: Antisense-mediated inhibition of Bc1-2 protooncogene expres-sion and leukemic cell growth and survival: compari-sons of phosphodiester and phosphorothioate oligodeoxynucleotides. CancerRes. (1990) 50:6565–6570.
  • BLOEM A, LOCKHORST H: Bc1-2 antisense therapy inmultiple myeloma. Pathol. Biol. (Paris) (1999) 47:216–220.
  • MORRIS M, TONG W, OSMAN I, et al: A Phase I/IIdose-escalating trial of Bc1-2 antisense (G3139) treatment by 14-day continuous intravenous infusion for patients with androgen-independent prostate cancer or other advanced solid tumor malignancies. Proc. Am. Soc. Clin. Oncol (1999) 18:323a.
  • MORRIS M, TONG W, WILLIAM P, et al.: A Phase I trial ofBc1-2 antisense drug G3139 (Genta, Inc.) delivered by continuous intravenous infusion alone or in combina-tion with weekly paclitaxel. Proc. 1999 AACR, NCI, EORTC International Conference. Washington, DC, USA (1999).
  • WATERS J, WEBB A, CUNNINGHAM D, et al.: Results of aPhase I clinical trial of Bc1-2 antisense molecule G3139 (GENTA) in patients with non-Hodgkin's lymphoma. Proc. Am. Soc. Clin. Oncol (1999) 18:4a.
  • WEBB A, CUNNINGHAM D, COTTER F, et al: Bc1-2 antisense therapy in patients with non-Hodgkin lymphoma. Lancet (1997) 349:1137–1141.
  • BLOEM A, LOCKHORST H: Bc1-2 antisense therapy inmultiple myeloma. Pathol. Biol. (Paris) (1999) 47:216–220.
  • LYON J, ROBINSON C, WATSON R: The role of Myb proteins in normal and neoplastic cell proliferation. Grit. Rev. Oncog. (1994) 5:373–388.
  • NAUMANN U, EISENMANN-TAPPE I, RAPP UR: The role ofRaf kinases in development and growth of tumors. Recent Results Cancer Res. (1997) 143:237–244.
  • HENRY SP, MONTEITH D, BENNETT F, LEVIN AA: Toxico-logical and pharmacokinetic properties of chemically modified antisense oligonucleotide inhibitors of PKC-alph a and C-raf kin ase. AntiCancer Drug Des. (1997) 12:409–420.
  • ••Exhaustive studies on ODN toxicology.
  • KERKHOFF E, RAPP UR: Cell cycle targets of Ras/Raf signalling. Oncogene (1998) 17:1457–1462.
  • MAGNUSON NS, BECK T, VAHIDI H, HAHN H, SMOLA U, RAPP UR: The Raf-1 serine/threonine protein kinase. Semin. Cancer Biol (1994) 5:247–253.
  • MONIA BP: First- and second-generation antisense inhibitors targeted to human c-raf kinase: in vitro and in vivo studies. Anticancer Drug Des. (1997) 12:327–341.
  • MONIA BP, JOHNSTON JF, GEIGER T, MULLER M, FABBRO D: Anti-tumor activity of a phosphorothioate antisense oligodeoxynucleotide targeted against C-raf kinase. Nature Med. (1996) 2:668–675.
  • MONTEITH DK, GEARY RS, LEEDS JM, JOHNSTON J, MONIA BP, LEVIN AA: Preclinical evaluation of the effects of a novel antisense compound targeting C-raf kinase in mice and monkeys. Toxicol. Sci. (1998) 46:365–375.
  • STEVENSON JP, YAO K, GALLAGHER M, et al.: Phase Iclinical/pharmacokinetic and pharmacodynamic trial of the c-raf-1 antisense oligonucleotide ISIS 5132 (CGP 69846A). J. Clin. Oncol (1999) 17:2227–2236.
  • STEVENSON JP, GALLAGHER M, RYAN W et al.: Phase Itrial of the c-Raf-1 antisense oligonucleotide (ODN) ISIS 5132 administered as a 21-day continuous W infusion in combination with 5-fluorouracil (5-FU) and leucovorin (LV) as a daily x 5 IV bolus. Proc. 1999 AACR, NCI, EORTC International Conference. Washington, DC, USA (1999) 118.
  • CHEN H, NESS E, MARSHALL J, et al: Phase I trial of asecond generation oligonucleotide (GEM231) targeted at Type I protein kinase a in patients with refractory solid tumors. Proc. Am. Soc. Clin. Oncol. (1999) 18:159a.
  • MCGRAW K, MCKAY R, MIRAGLIA L, et al.: Antisenseoligonucleotide inhibitors of isozymes of protein kinase: in vitro and in vivo activity and clinical development as anti-cancer therapeutics. AntiCancer Drug Des. (1997) 12:315–327.
  • HOLMLUND J, NEMUNAITIS J, SCHILLER J, DORR A,KISNER D: Phase I trial of c-raf antisense oligonucleo-tide ISIS 5132 (CGP69846A) by 21-day continuous intravenous infusion (CIV) in patients with advanced cancer. Proc. Am. Soc. Clin. Oncol. (1998) 17:210a.
  • HOLMLUND J, RUDIN C, MANI S, et al.: Phase I trial of ISIS5132 /ODN 698A, a 20-mer phosphorothioate antisense oligonucleotide inhibitor or c-raf kinase, administered by a 24-hour weekly intravenous infusion to patients with advanced cancer. Proc. Am. Soc. Clin. Oncol (1999) 18:157a.
  • KIRSCHNER LS, CARNEY JA, PACK SD, et al. Mutations of the gene encoding the protein kinase A Type I-alpha regulatory subunit in patients with the carney complex. Nat. Genet. (2000) 26(0:89–92.
  • NESTEROVA M and CHO-CHUNG YS. A single-injection protein kinase A-directed antisense treatment to inhibit tumour growth. Nat. Med. (1995) 1 (6):528–533.

Websites

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.