Construction Of M-CSFr DNA Vaccine And Investigations Of Its Anti-tumor Immune Responses

Tumor DNA vaccination is a novel strategy for the inununotherapy of tumors, which targets the tumor associated antigen (TAA). It is constructed by directly cloning a specific gene fragment encoding TAA into a mammalian expression vector, and this "naked" DNA construction is used to immunize the host. Tumor DNA vaccine works like a live virus infection, which can transfect the host cells, and then transcript and translate its encoding TAA. The synthesized TAA can be up-taken and presented to immune system by APC of the host, which results in the activation of T cells, and consequently elicits TAA specific antibody and CTL responses.Since Conry and his colleagues constructed the first tumor DNA vaccine (CEA polynucleotide vaccine), more than 20 types of tumor DNA vaccines have been extensively investigated over the world. So far, it is encouraging that six types of tumor DNA vaccines have been approved by FDA for phase I/II clinical trials in USA, including gp 100 and TRP-2 DNA vaccines for melanoma, CEA DNA vaccine, HPV E6 and E7 DNA vaccines for cervical carcinoma, MUC1 DNA vaccine for breast cancer, Anti-idiotypic DNA vaccine for lymphoma and PSA DNA vaccine for prostate cancer.Macrophage colony-stimulating factor receptor (M-CSFr), a transmenbrane protein encoded by the c-fms proto-oncogene, is an important member of the receptor tyrosine kinase family. It has been established that the aberrant expression or mutation of c-fms is implicated in the pathogenesis of several solid tumors, as well as leukemia and MDS. Co-transfer of c-fms and its ligand (M-CSF) gene into NIH3T3 cells can lead to its transformation and tumorigenesis. Taken together, it is obvious that the c-fms proto-oncogene is implicated in tumorigenesis, and that its product M-CSFr might be a potential target for the immunotherapy of tumors.