Radiation-Induce Immune Modulation in Prostate Cancer
Annual rept. 1 Jan-31 Dec 2004
CALIFORNIA UNIV LOS ANGELES
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This proposal is designed to determine if radiation therapy inhibits presentation of prostate tumor antigens through the endogenous pathway by dendritic cells DC and to devise strategies to overcome this inhibition. This functional immune suppression following radiation therapy is not associated with cell killing but rather by interference with antigen processing. In this regard it is very different from the conventional view of immune suppression associated with lymphocyte sensitivity to radiation. The experiments will be performed within a humanized murine system for easy translation to the clinic. We chose to study responses to PSA, but given the high risk involved in these experiments and because PSA is so highly expressed in serum of patients with human prostate cancer, we decided to evaluate responses to a second antigen that is highly expressed in prostate cancer, survivin, as a back-up. The plan is to attempt to blunt radiation-induced immune suppression using IL-3 andor GM-CSF to stimulate DC. Most of the first year has been spent developing reagents that can be used experimentally and refining protocols in particular for DC purification, which maximizes effects. This phase is now nearing completion, and we have initiated the murine experiments.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research
- Anatomy and Physiology