A PHASE I/II STUDY OF IMMUNIZATION WITH LYMPHOTACTIN AND INTERLEUKIN 2 GENE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We intend to test the safety, and immunologic and clinical efficacy of a combination of 2 allogeneic neuroblastoma tumor cell line vaccines, one of which has been genetically modified to secrete the cytokine/chemokine combination of IL-2 and lymphotactin, in patients undergoing chemotherapy for newly diagnosed, high risk neuroblastoma who receive single autologous stem cell rescue as consolidation therapy. This protocol will be carried out as a Phase I/IIa study to evaluate the safety and toxicity of adding a previously unstudied, unmodified, irradiated neuroblastoma cell line (SKNLP) to a studied, safe dose of a gene modified, IL-2/Lptn secreting neuroblastoma cell line SJNB-JF-IL2/Lptn to be given as a vaccine to patients diagnosed with high risk neuroblastoma. HYPOTHESIS We hypothesize that immunization with the unmodified SKNLP in conjunction with IL2/Lptn gene modified SJNB-JF cell lines will provide an effective and measurable immune response against neuroblastoma, resulting in diminished minimal residual disease and improved progression free and overall survival in patients with high-risk neuroblastoma. In the absence of randomization, we will not be able to state definitively whether any loss of MRD is attributable to the transplant or to the additional immunization schedule, but a progressive reduction in MRD occurring over the duration of the immunization period, associated with a developing immune response against the tumor, will favor a contribution from the experimental therapy. Moreover, if patients lose their anti-tumor immune response when the course of vaccination is complete, and MRD subsequently returns, then this will further support our hypothesis. SPECIFIC AIMS Primary Objectives: 1. Evaluate the safety of repeated immunization with gene-modified, IL-2 lymphotactin secreting SJNB-JF-IL2 and SJNB-JF-Lptn cells co-administered with the unmodified SKNLP neuroblastoma cell line. 2. Evaluate the immune response to these immunizations. 3. Evaluate changes in minimal residual disease load by polymerase chain par Secondary Objectives: 1. Estimate 3 year progression free survival (PFS) and overall survival (OS) in vaccinated patients.