Vectors for Treatment of Metastatic Breast Cancer
Final rept. 15 Jul 2003-14 Jul 2006
SIDNEY KIMMEL CANCER CENTER SAN DIEGO CA
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The objective is to design, build and study vectors which would be able to break tolerance to breast cancer associated TAA and to be used to suppress the recurrence of metastatic breast cancer following surgical resection. The hypothesis is that by fusing the CD40 ligand stripped of its transmembrane domain and intracytoplasmic domains, to a breast cancer TAA such as the extracellular domain of the her-2-neu receptor, or the extracellular tandem repeat peptides of breast cancer associated surface glycoprotein, MUC-1 both of which have been shown to be capable when loaded on APCs of conferring resistance to engraftment by cancer cells bearing these TAA, one can break tolerance to breast cancer. The subcutaneous injection of this vector creates infected cells as factories to secrete the CD40LTAA into the systemic circulation as well as locally for the activation and antigen loading of APCs, so that they would move to the lymph nodes all over the body to generate the CD8 dependent response against metastatic breast cancer. We also explored boosting of the vector vaccine by TAACD40L protein injections. This report summarizes the successful assembly and study of these vectors. These injections break tolerance to tumor associated antigens in mouse models.
- Medicine and Medical Research