UF Health Department of Radiology The Department of Radiology at UF Health Shands Hospital consists of a large imaging facility for both inpatients and outpatients . The Neuroradiology Department will review all the radiological procedures in this proposal and be available to discuss the interpretation of any MRI findings that may be confusing in the setting of combinatorial therapy. UF Health Brain Tumor Biorepository This Biorepository or “tissue bank” has successfully obtained and stored brain tumor tissue and matched peripheral somatic cells from individual brain tumor patients. There are also peripheral somatic cells stored from non-brain tumor disease control patie nts and normal subjects. Personnel from the Brain Tumor Biorepository will sterilely divide material from the operating room and preserve according to IRB approved biorepository protocol and SOPs . All patient information is entered into database at which time the program will generate a unique number for the specimen. Outside Laboratories Accredited outside laboratories used in patient assessment will be registered using Form FDA 1572 (21 CRF 312.53(c)). 21. DATA ANALYSIS Samples collected from subjects dur ing the phase 1 trial (FDA IND BB 14058; Duke IRB Pro00018020; PI: Duane A. Mitchell) will be analyzed as described below. Patients treated at the phase 2 established dose of T cells (3x107 cells/Kg) may be included in the statistical analysis summary. Patients treated below the targeted dose will be included in a descriptive analysis only. 21.1 Progression Free Survival (PFS) and Overall Survival (OS ) The study statistician will be responsible for all statistical analysis. Estimating the potential efficacy of adoptive transfer with TTRNA -xALT plus TTRNA -DCs will be the primary goal of this Phase I/II evaluation. Patients enrolled on this study who are confirmed to have a reMB/PNET will be followed for all parameters until death. T he Kaplan -Meier estimator will be used to describe the progression- free survival and OS experience of vaccinated patients from the initiation of HDC as this is within 24hrs of the frame of reference for our historical control comparison (PBSCT defined as Day 0 in historical control cohort) . We will define the PFS and OS from the time of proximal tumor recurrence as a clinical reference point for further comparison to other treatment regimens within the published literature. We do not anticipate any appr eciable data lost during this study due to premature patient drop out or lost to follow up. 21.2 Radiographic Response and Progression Criteria for Patients with Residual Disease All radiographic responses will be based on MRI scans of the brain and spine obt ained with and without contrast. Tumor size will be based on the product of the maximal diameters in 2 different planes. Response will be assessed as a percentage change in tumor size from baseline. Tumor measurements in the follow -up scans will Re-MATC H Protocol Page 84 of 106 Version: 20180628 be compared to those of the pre -treatment (baseline) scan to document response. However, determination of progressive disease will be based on comparison of the current tumor dimensions with the smallest measurements of the tumor recorded since the start of treatmen t. The assessment of steroid dose as “stable or tapering” will be based on the dose the patient was receiving on the day of the follow -up scan with that on the day of the pre -treatment scan. Residual disease will be defined as contiguous contrast enhanceme nt ≥ 1 cm2 (product of measurement obtained in 2 perpendicular planes (i.e., axial and coronal) ). For residual disease present at the time of the last MRI prior to initiating vaccination, radiographic response will be evaluated based on the NCI-endorsed, World Health Organization RECIST criteria and using a modified version of the MacDonald criteria [7,8] which is outlined below. Complete Response Complete disappearance of enhancing tumor on consecutive CT or MRI images at least 8 weeks apart, and neurologically stable or improved and at a stable or a lower steroid dose. If CSF cytology was previo usly positive, it should now be negative. To be assigned a status of “Complete Response” as a best overall response, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 8 weeks after the criteria for response is first met. Partial Response At least a 50% reduction in tumor size on consecutive MRI images at least 8 weeks apart, and neurologically stable or improved and at the same or a lower steroid dose. If CSF cytology was previously positive, it should now be negative. To be assigned a status of “Partial Response” as a best overall response, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 8 weeks after the criteria for response is first met. Stable Disease Insufficient change to qualify for Partial Response or Progressive disease. CSF cytology remains positive or becomes negative. Progressive Disease At least a 2 5% increase in the longest diameter on an axial image of any enhancing contiguous tumor on consecutive CT or MRI images. CSF cytology may be positive or negative. Not Assessable Progression has not been documented and one or more sites have not been assessed. 21.3 Radiographic Response and Progression Criteria for Patients with Complete Resection A complete resection will be defined as contiguous contrast enhancement < 1 cm in 2 perpendicular measurements in each of 2 perpendicular planes (i.e., axial and coronal). Because neither the RECIST [ 8] nor MacDonald [7] criteria are completely appropriate for patients with minimal residual disease, a modified version of these criteria will be used as outlined below. Complete Response Complete disappearance of enhancing tumor on consecutive CT or MRI images at least 1 month apart, and neurologically stable or improved and at the same or a lower steroid dose. To be assigned a status of “Complete Response” as a best overall response, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response is fir st met. Partial Response At least a 30% reduction in longest diameter on an axial image of any contiguous enhancing tumor on consecutive CT or MRI images at least 1 month apart, and neurologically stable or improved and at the same or a lower steroid dose . To be assigned a status of “Partial Response” as a best overall response, changes in tumor Re-MATC H Protocol Page 85 of 106 Version: 20180628 measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response is first met. Stable Disease Insufficient change to qualify for Partial Response or Progressive disease. Progressive Disease At least a 20% increase in the longest diameter on an axial image of any enhancing tumor on consecutive CT or MRI images with a minimum of ≥ 5 mm of contiguous contrast enhancement in 2 perpendicular measurements in each of 2 perpendicular planes (i.e., axial and coronal). Not Assessable Progression has not been documented and one or more sites have not been assessed. 21.4 Special Circumstances  If a scan is suspicious but not definitive for progressive disease (including indeterminate lesion size or enhancement that is not clearly disease progression) in the absence of clinical progression, an investigator may elect to confirm progression through alternate means, including biopsy, or repeat MRI at 4 -8 weeks, symptomatic follow up or other modalities. o Protocol treatment will continue until the investigator considers progression documented.  Disease that was measurable at baseline and appeared to be one solid mass splits to become 2 or more smaller lesions o note that the lesion has split, to identify the separate lesions as unique and to record the measurements of each. o appearance of these individual split lesions will not automate a response assignme nt of PD; they will contribute to a determination of progression only if the sum of all lesions meets the criteria for PD.  2 or more lesions which were distinctly separate at baseline become confluent at subsequent visits o note the occurrence and capture t he required measurement(s) of the confluent mass.  A required region of a baseline scan may be unavailable or technically inadequate, and 1 or more lesions are detected on a subsequent scans. o Such lesions are identified as additional evaluable lesions that do not contribute to determination of that visit’s response. o If at a successive time point disease progression is noted, the overall response per time point will be PD. o For those areas inadequate at baseline, the first scan available will become the refer ence scan by which later scans are compared for evaluable progression.  1 or more lesions are detected in regions unavailable or inadequate at baseline that were also not required o regarded as new lesions, resulting in an overall response of PD for that time point.  Regions are not available or adequate at post -baseline visit assessments that showed disease at baseline o an overall response of NA will be assigned to that visit unless other available data shows progression. Re-MATC H Protocol Page 86 of 106 Version: 20180628 Overall Response Measurable Lesions Evaluable Lesions New Lesions Overall neurological status Steroid Use Additional notes PD PD PD Yes Unequivocal worsening Stable or increased use PD by any single component (not steroids by criteria) no sooner than 1 month after the first course of treatment SD All other combinations, but please note the following particular combinations: CR, PR or SD CR or SD No NA Off steroids, stable dose Note that a lack of steroid or neurological information could prevent CR or PR from being recorded CR, PR or SD CR or SD No improved, unchanged, possible worsening NA Note that a lack of steroid or neurological information could prevent CR or PR from being recorded NA NA NA improved, unchanged, possible worsening Off steroids, stable use CR, PR or SD CR or SD No improved, unchanged, possible worsening Off steroids, stable dose A CR or PR overall response assignment is not possible with a neurological grading of -1. PR PR or CR CR or SD No unchanged or improved Off steroids, stable use All conditions need to apply and CR criteria do not apply. CR CR CR No unchanged or improved Off steroids All conditions need to apply. NA NA NA NA NA Off steroids, stable dose NA applies when NA is true of both radiology and neurological status. Re-MATC H Protocol Page 87 of 106 Version: 20180628 21.5 Survival Survival is not an endpoint in this study but will be accessioned to derive hypotheses that may relate data obtained in this study with survival times. Survival will be calculated from the date diagnostic tissue confirming recurrence is first obtained and also from the time of Vaccine #1 for both Groups A and B. Identification of Covariates Descriptive statistics (e.g. frequencies and means/SD) will be used to summarize levels of polyfunctional T cells, cytotoxic T cell responses, tumor -specific antibodies, and serum cytokine levels in the peripheral blood measured bimonthly. Specifically, we will address the hypothesis that polyfunctional tumor -specific T cell responses may be important for mediating clinical efficacy of DC + xALT therapy. Hotelling’s t- statistic will be used to determine whether changes in the polyfunctional T cells occurred during the 3 initial vaccinations. Cox proportional hazards model will be used to assess the effect of the pre -vaccination level of polyfunctional T cell on PFS -12 a nd OS with and without adjustment for known prognostic factors. The change observed in polyfunctional T cells during the first 3 vaccinations will be computed and its relationship with PFS -12 and PFS beginning at the time of the third vaccination with and without adjustment for known prognostic factors. Similar analyses may be conducted examining changes between pre- vaccination and other monthly follow -up assessments. The use of time -dependent variables within the Cox model for PFS -12 and OS beginning pr e- vaccination will be explored. Logistic regression will be used to predict PFS -12 and 2yr -OS as a function of baseline polyfunctional T cell counts and previously defined changes. Given the large number of predictors that will be examined relative to th e overall sample size, it is recognized that these analyses will be exploratory.