CTLA-4 Blockade-Based Immunotherapy in Prostate Cancer
Abstract
CTLA-4 is an inhibitory molecule on T cells down regulation. Granulocyte-macrophage colony stimulating factor (GM-CSF) is a growth and survival factor for dendritic cells. The safety of combining GM-CSF with CTLA-4 blockade in prostate cancer patients is being investigated in an ongoing phase 1 trail. Sequential cohorts of 3-6 patients receive GM-CSF 250 ug/m2/d subcutaneously on days 1-14 of a 28-day cycle with escalating doses of anti-CTLA antibody on day 1 of each cycle x4. Patients are monitored for clinical autoimmunity with T cell phenotyping performed. Twelve patients have been treated to date. Dose-limiting toxicity (DLT) was not observed in the initial CTLA-4 antibody dose level. Two DLTs, consisting of a vertebrobasilar TIA possibly related to therapy and a generalized rash requiring steroids were observed in the second and third dose levels respectively, resulting in expansion of each to 6 patients. No laboratory evidence of autoimmunity has been observed in any patient. Expansion of monocytes/dendritic cells and upregulation of PBMC activation markers have been seen, consistent with known GM-CSF effect. CTLA-4 blockade and GM-CSF has demonstrated preliminary safety in advanced prostate cancer. Accrual and immunologic analyses are ongoing.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2005
- Accession Number
- ADA433986
Entities
People
- Brian I. Rini
Organizations
- University of California, San Francisco