623. Polymer Microparticles Delivering a Idiotype/Chemokine Fusion DNA Vaccine Generate Protective Immunity in a Mice Model of B Cell Lymphoma
Year: 2006
Type: article
Abstract: Dendritic cell (DC)-based cancer immunotherapy has been suggested to hold potential to treat various kinds of malignancies, however, the current clinical studies suggest some issues including the requirement of optimized activation of DCs.We recently revealed that F-deficient non-transmissible recombinant Sendai virus (SeV/ dF) could activate human and murine DCs inducing strong antitumor effects on subcutaneously inoculated tumors.For further assessment, we assessed the preventive effect of SeV/dF to a rat model of spontaneous metastasis of prostate cancer. EXPERIMENTAL DESIGNS:The AT6.3 cells, highly metastatic, androgen-independent anaplastic subline from Dunning R-3327 rat prostate adenocarcinoma, served as models for spontaneous metastasis after intradermal tumor inoculation at left lateral flank.DCs were generated from bone marrow of Copenhagen rat by culturing in the presence of GM-CSF and IL-4, and were pulsed with SeV and tumor lysate, and 3x10 6 mature DCs, which was insufficient cell number to suppress the local tumors, were then administered via intratumor (skin) or intravenous (tail vein) routes. RESULTS:As representative results, primary tumor volume of each group was not affected at all by DC treatment of relatively small number during the experimental course.Interstingly, on the other hand, numbers of spontaneous lung metastatic nodules (P=0.0384 and P=0.0028, respectively) as well as lung volumes (P=0.0213 and P=0.0028, respectively), were dramatically reduced in both SeV/dF-DC treatment groups.The antitumor effect of intravenous administration of SeV/dF-DCs was more pronounced than that seen in intratumor injection.Tumor-antigen specific T-cell proliferation was confirmed as corresponding to the antitumor effect in SeV/dF-DC treated rat. CONCLUSIONS:Even though the relatively small number of SeV/dF-DCs, which was not sufficient to control preestablished dermal tumor, was used, SeV/ dF-activated DCs effectively prevented spontaneous lung metastasis of prostate cancer.These results thus suggest that cancer immunotherapy using SeV/dF-DC may has a potential as a novel approach to treat systemic spread of prostate cancer. 623.
Source: Molecular Therapy
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W1992503932