Genetically Engineered Autologous Cells for Antiangiogenic Therapy of Breast Cancer

摘要

Cancer growth and spread depends on the orchestrated proliferation of tumor-associated blood supply. Cancer cells release signals that instruct the body to build new blood vessels, angiogenesis, required to feed the tumor as it increases in size. Pharmacological agents, i.e. proteins and derivatives, that interfere with angiogenesis, in cancer bearing mice, stop cancer growth and lead to its regression. Animal modeling has revealed that repeated administration of large amounts of such antiangiogenic proteins is required for anti- cancer effect. This may be logistically difficult to achieve in larger beings such as humans. A remedy to this problem would involve a combined cell and gene therapy approach. We propose that normal tissue such as marrow stromal cells (MSCs) can be harvested from patients, genetically engineered, and subsequently returned to the patient as an implant releasing on a continuous basis therapeutic proteins that interfere with cancer growth and spread. We have already developed and published most of the key components required to develop this novel therapeutic modality, such as vectors, MSCs, and matrices. Also thus far, we have shown significant decrease in tumor progression over time with Interleukin-l2-secreting MSCs in the 4T1 mouse model of breast cancer and ascertained reproducibility of these results.