Scientific Achievements

PROJECT 2: THERAPEUTIC EFFICACY AND ANTI-TUMOR MECHANISMS EGFR ANTI-SENSE GENE THERAPY

Principal Investigator: Jennifer R. Grandis, MD

Scientific Achievements include:

  1. Approval of NGVL to manufacture the therapeutic antisense gene and identification of resources to support the manufacture
  2. Implementation of the phase I EGFR antisense gene therapy clinical trial. Five patients enrolled to date. First dose tier completed. One patient with disease progression requiring intubation and mechanical ventilation thereby necessitating removal from study.
  3. DSMB and IRB audit of study found no violations with approval to proceed.

Related Publications:

Zeng Q, Dhir R, Kanter PM, Huang L, Rubin Grandis J: Lack of toxicity of EGFR antisense gene therapy. J Exp Ther and Oncology 2(3): 174-186, 2002.
Lui VWY, Rubin Grandis J: EGFR-Mediated Cell Cycle Regulation. Anticancer Research 22; 1-12, 2002.
Riedel F, Götte K, Li M, Hörmann K, Grandis JR: EGFR antisense treatment of human HNSCC cell lines results in downregulation of VEGF expression and decreases endothelial cell migration in vitro. International Journal of Oncology 21(1): 11-6, 2002.
Li M, Ye C, Feng C, Reidel F, Liu X, Zeng Q, Grandis JR: Enhanced antiangiogenic therapy of squamous cell carcinoma by combined endostatin and epidermal growth factor receptor-antisense therapy. Clinical Cancer Research 8(11): 3570-3578, 2002.
Xi S, Rubin Grandis J: Gene therapy for the treatment of oral cancer. J Dental Res 82(1): 11-16, 2003.
Ford A, Grandis J: Targeting epidermal growth factor receptor in head and neck cancer. Head and Neck 25: 67-73, 2003.
Khalil MY, Grandis JR, Shin DM: Targeting epidermal growth factor receptor: a novel therapeutics in the management of cancer. Expert Rev Anticancer Research 3(3), 367–380, 2003.
Thomas SM, Zeng Q, Kanter PM, Watkins SF, Suscovich T, Rubin Grandis J: Tissue distribution of EGFR antisense gene therapy. Cancer Gene Ther 10, 518-528, 2003.
Niwa H, Wentzel AL, Li M, Gooding WE, Lui VWY, Grandis JR: Antitumor effects of EGFR antisense oligonucleotides in combination with Docetaxel in SCCHN. Clinical Cancer Research 9, 5028-5035, 2003.
Riedel F, Gotte K, Hormann K, Mengfeng Li, Rubin Grandis J: EGFR antisense treatment of human HNSCC cell lines results in downregulation of VEGF protein expression and endothelial cell migration. Int J Oncol 23(3): 577-583, 2003.
Pomerantz R, Rubin Grandis J: The role of epidermal growth factor receptor in squamous cell carcinoma of the head and neck. Current Oncology Reports. 5:140-146, 2003.
Lazo JS, Rubin Grandis J: Gene Therapy. Modern Pharmacology with Clinical Applications. 58:666-673, 2003.
Rubin Grandis J, Sok J. Signaling through the epidermal growth factor receptor during the development of malignancy. Pharmacology & Therapeutics 102:37-46, 2004.
Thomas SM, Rubin JR: Pharmacokinetic and pharmacodynamic properties of EGFR inhibitors under clinical investigation. Cancer Treatment Reviews 30:255-268, 2004.
Coppelli, FM, Rubin Grandis J: Oligonucleotides as anticancer agents: from the benchside to the clinic and beyond. Current Pharmaceutical Design, in press, 2004.
Pomerantz R, Rubin Grandis J: The epidermal growth factor receptor signaling network in head and neck carcinogenesis and implications for targeted therapy. Seminars in Oncology, in press, 2004.