Immunotherapy of Breast With Tumor RNA Transfected Dendritic Cell Vaccines

摘要

The goal of this grant was to develop effective treatments for patients with low volume metastatic disease using dendritic cell (DC)-based vaccines loaded with tumor RNA. The proposed studies were based on our previous findings that RNA loaded DC of murine and human origin are highly effective stimulators of T cells and tumor immunity. Toward this end, we have developed a robust procedure for generating immunopotent DC from breast cancer patients and methods to isolate and amplify RNA from small amounts of tumor cells were developed. Efficient loading of DC with RNA was accomplished by electroporation. To differentiate ('mature') DC we developed a novel approach whereby incubation of the DC with biological response modifiers (i.e., soluble CD40 ligand) is replaced by transfection with the corresponding mRNA. The tumor RNA loaded DC were highly effective at stimulating CTL responses in vitro. Optimized and reproducible protocols were developed for the planned clinical trials. IRB approval and IND were obtained for a phase I clinical trial in breast cancer patients. The trial has not been yet initiated due to accrual difficulties.