This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Neuroblastoma is a form of pediatric cancer that leads to significant morbidity and mortality. As the 2nd most common malignant solid tumor, it accounts for greater than 10% of all pediatric cancer deaths. With current therapy, overall survival remains less than 30-40% for patients with stage 4 high-risk disease and there is an urgent need for improved treatments options for these children. We and other groups have show immunological and clinical efficacy with the use of neuroblastoma-specific immunotherapy. Due to the heterogeneous nature of neuroblastoma, teaching the immune system to target a diverse tumor antigen repertoire and use a broader array of host effector mechanisms with the use of tumor cell vaccines may provide increased anti-tumor efficacy when compared to adoptive cellular and monoclonal antibody therapy. During our last allogeneic tumor cell vaccine trial, we were able to induce clinical responses, including complete remissions, in patients with relapsed/refractory disease. However, the overall results were likely limited by the number of tumor antigens presented and the inhibitory microenvironment of the tumor. In this clinical study, we propose to address these obstacles by 1) modifying the vaccine product to increase the number of tumor associated antigens presented to the immune system, and 2) combine vaccination with metronomic oral cytoxan which has been show to alter the tumor microenvironment via anti-angiogenesis and suppression of T regulatory cells.
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