Phase I Trial of Adenovirus-Mediated IL-12 Gene Transduction in Patients with Recurrent Locally Advanced Prostate Cancer Following Therapy
Abstract
Patients with radiorecurrent prostate cancer have few options. Gene therapy may define a treatment option of both local and systemic value. Pre-clinical studies using adenovirus-mediated (Ad.) transduction of IL-12 (Ad.mIL-12) in a metastatic model of prostate cancer resulted in local growth suppression, survival enhancement and inhibition of pre-established metastases. The basis for these activities include the induction of both innate (neutrophils & NKs) and acquired immunity (T cells). On the basis of these results, we propose to explore the use of Ad.hIL-12 in patients with clinically localized radiorecurrent prostate cancer in a Phase I trial to explore the safety, induction of immune responses and efficacy following therapy. Specific Aims/Study Design: In Aim I patients will be placed in escalating dose cohorts with the primary endpoint of the maximum tolerated dose as determined by physical examination, laboratory values of bodily functions and evidence of IL-12 gene transduction by measurement of serum by ELISA.. In Aim 2 additional safety data will be recorded through measurement of serum levels of the pro-inflammatory cytokines, TNF- , IFN- and IL-16 by ELISA. In Aim 3 peripheral blood mononuclear cells (PBMCs) will be screened for the induction of T cells, which target the prostate antigens, PSA and PAP via an ELISPOT assay.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2005
- Accession Number
- ADA474987
Entities
People
- Simon J. Hall
Organizations
- Icahn School of Medicine at Mount Sinai