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ADVANCES IN CLINICAL GENE THERAPY 1159 A Phase I/II Study of High Dose Allogeneic GM-CSF Gene-Transduced Prostate Cancer Cell Line Vaccine in Patients with Metastatic Hormone-Refractory Prostate Cancer Natalie Sacks,1 Eric Small,2 Celestia Higano,3 John Corman,4 Arthur Centeno,5 David Smith,6 Christopher Steidle,7 Marc Gittelman,8 Kendrith Rowland,9 Gary Hudes,10 Jonathan W Simons,11 Eugene Dula,12 Jay Young,13 Dale Ando.1 Clinical Research, Cell Genesys, Inc., Foster City, CA; University of California at San Francisco, San Francisco, CA; Seattle Cancer Care Alliance, Seattle, WA; 4Virgina Mason Medical Center, Seattle, WA; 5Urology San Antonio Research, San Antonio, TX; 6Department of Hematology/Oncology, University of Michigan Medical Center, Ann Arbor, MI; 7Northeast Indiana Research, Fort Wayne, IN; 8South Florida Medical Research, Aventura, FL; 9Carle Cancer Center, Urbana, IL; 10Seattle Cancer Care Alliance, Seattle, WA; 11Fox Chase Cancer Center, Philadelphia, PA; 12Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA; 13West Coast Clinical Research, Van Nuys, CA; 14South Orange County Medical Research Center, Laguna Woods, CA Phase II studies show treatment with allogeneic prostate carcinoma cell lines (PC-3 and LNCaP) genetically modified to secrete GM-CSF (GVAX® Prostate Cancer Vaccine) can delay time to progression and prolong survival to a median of 31 months with a 300 million cell dose v 22 months with a 100 million cell dose in patients with metastatic antiandrogen refractory prostate cancer (Proc ASCO, Vol 21:183a, 2002) Given these dose response data as well as the absence of any dose limiting toxicity, GVAX® Prostate Cancer Vaccine has been re-engineered to secrete GM-CSF at higher levels and is the subject of ongoing clinical evaluation 65 patients with metastatic hormone refractory disease have been treated in a dose-escalation trial designed to optimize the dose and schedule of administration for Phase III trials Escalating doses of vaccine of 100, 200, 300 and 500 prime/300 million cells at bi-weekly or monthly intervals for months were evaluated In 33 evaluable patients treated on a monthly outpatient vaccination schedule for months, no dose limiting toxicities were observed; consistent with previous GVAX® cancer vaccine trials, injection site reactions have been the most common adverse event One patient had a partial PSA response, and had minor PSA responses ICTP (serum carboxyterminal telopeptide of type I collagen) was measured as a validated molecular surrogate for osteoclast activation/bone metastasis progression in men with advanced prostate cancer In the first 15 patients treated, the ICTP level decreased in five patients (33%); in 2/5 ICTP levels were reduced to undetectable post treatment Normalization of pathophysiologic osteoclast activity in metastases suggests a novel mechanism of prostate GVAX® immunotherapy Updated data on patients treated with bi-weekly vaccinations from this ongoing clinical trial, and ICTP responses, will be presented Phase III trials are planned with this high potency allogeneic cell-based prostate cancer vaccine N Sacks and D Ando are employees of Cell Genesys 1160 A Phase I Clinical Trial with OncoVEXGM- CSF Jennifer Hu,1 Iain McNeish,1 Claire Shorrock,2 Jan Steiner,3 Colin Love,2 Robert Coffin,2 Charles Coombes.1 Hammersmith Hospital Campus, Imperial College of Science and Medicine, London, United Kingdom; 2BioVex Ltd, Abingdon, Oxon, United Kingdom; 3Oxford Therapeutics Consulting, Oxford, Oxon, United Kingdom This abstract reports an ongoing Phase I clinical trial with OncoVEXGM-CSF, which is, we believe, the first oncolytic virus that Molecular Therapy Vol 7, No 5, May 2003, Part of Parts Copyright ® The American Society of Gene Therapy also contains an active gene to enter clinical trials OncoVEXGM-CSF is an oncolytic herpes simplex virus (HSV) which has demonstrated enhanced pre-clinical anti-tumour potency as compared to previous oncolytic HSV The virus is based on a primary isolate of HSV which replicates more effectively in human tumour cells than the laboratory strains used elsewhere Deletion of ICP34.5 provides tumour selective replication Additionally ICP47 is deleted and the gene for human GM-CSF inserted to boost the anti-tumour immune response following liberation of tumour antigens by virus replication OncoVEXGM-CSF provides, therefore, an in situ, patient specific, GMCSF enhanced, anti-tumour vaccine combined with oncolysis, and is intended to treat both injected tumours and disseminated disease In the clinical trial, OncoVEXGM-CSF is being tested by direct injection in cutaneous and sub-cutaneous metastatic deposits of a number of tumour types (breast cancer, melanoma, head and neck cancer and certain gastro-intestinal cancers) The clinical trial is a dose escalation study in groups of four patients at three dosage levels, followed by a multi-dosing phase in cohorts of patients, in which safety is the primary end point Evidence of biological activity is also being collected including histological observation of cellular infiltrates, measurement of cytokine levels, and gross observation of injected and un-injected tumours So far eleven patients have been treated at 106, 107 and 108 pfu These doses have been well tolerated PCR has shown detectable virus in blood and/or urine in a subset of patients which is cleared