7. OBJECTIVES/SPECIFIC AIMS/STUDY QUESTI ONS 7.1 Hypotheses • Our MAIN HYPOTHESIS is that: o Adoptive transfer of tumor -specific lymphocytes coupled with TTRNA -pulsed DC vaccinations that target reMB/PNETs will lead to the safe eradication of residual tumor cells during hematopoietic recovery from myeloablative and non- myeloablative chemotherapy and autologous PBSCT. • SECONDARY HYPOTHESES that will be explored in this study are that: o Treatment of pediatric patients with reMB/PNETs using TTRNA -xALT and TTRNA - DCs will enhance polyfunctional anti -tumor T cell responses o Treatment of pediatric patients w ith reMB/PNETs using TTRNA -xALT and TTRNA - DCs extends progression free survival (PFS) compared to a historical cohort . o A correlation exists between persistence of anti -tumor immunity and clinical outcome in patients with reMB/PNETs o Myeloablative and NMA chemotherapy will lead to increases in homeostatic and inflammatory cytokines, decreases in circulating CD4+CD25+FOXP3+ T regs, as well as increases in TLR activation in patients with reMB/PNETs 7.2 Study Objectives • PRIMARY OBJECTIVE S for the PHASE II Trial : o To determine if DC + xALT therapy extends progression -free survival compared to historical benchmarks during recovery from HDC + PBSCT (Group A) or salvage chemotherapy (Group B) in pediatric patients with reMB/PNETs • SECONDARY OBJECTIVES o To determine the objective radiographic response rate of MA and NMA chemotherapy coupled with DC + xALT therapy in patients with residual disease o To determine if magnitude and persistence of anti -tumor humoral or cellular immunity correlates with clinical outcome o To evalu ate changes in cytokine profile and Toll -Like Receptor (TLR) activation status in pediatric patients with reMB/PNETs after HDC (Group A) or salvage chemotherapy (Group B) and during DC + xALT therapy Re-MATC H Protocol Page 41 of 106 Version: 20180628 o To characterize the immunologic phenotype of lymphocyte subsets (naïve, effector, memory, regulatory) and NK cells in patients with reMB/PNETs at diagnosis and during experimental therapy o To identify potential tumor specific antigens as vaccine candidates through characterizing the frequency of expression of the top 40 tumor associated antigens (TAA 40) identified in common malignancies in recurrent MB/PNETs o To determine the progression- free survival and overall survival rate in pediatric patients with recurrent MB/PNETs receiving DC + xALT therapy after HDC pl us PBSCT (Group A) compared to a historical benchmark o To determine the progression- free survival and overall survival rate in pediatric patients with recurrent MB/PNETs receiving DC + xALT therapy after salvage chemotherapy (Group B) compared to a historic al benchmark 8. STUDY DESIGN This will be a dual -arm prospective multi -institutional Phase II clinical trial where the 12- month progression- free survival rate in each group will be compared to a historical benchmark.