Intra-Tumoral Injections of Natural Killer Cells for Recurrent Malignant Pediatric Brain Tumors

PRIMARY OBJECTIVES: I. To determine the safety and tolerability of natural killer (NK) cells that have been propagated ex vivo with genetically-modified feeder cells and administered intra-tumoral via an Ommaya reservoir in participants with recurrent or progressive malignant brain tumors. II. To determine the recommended phase 2 dose (RP2D) for natural killer (NK) cells that have been propagated ex vivo with genetically-modified feeder cells and administered intra-tumoral via an Ommaya reservoir in participants with recurrent or progressive malignant brain tumors. EXPLORATORY OBJECTIVES: I. To determine the 6 months overall survival (OS), defined as the percentage of participants in the study who are alive at 6 months following start of treatment. II. To determine the persistence, immuno-phenotype and function of adoptively-transferred expanded NK cells and correlate the findings with the overall response. III. To determine the immune signature-based profile of each patient's tumor. IV. To determine changes in the T-cell receptor (TCR) repertoire diversity before and after Transforming growth factor beta imprinted (TGFβi) NK cell treatment. V. To evaluate the effect of systemic steroids on the persistence and efficacy of TGFβi NK cells. VI. To assess Quality of Life (QOL) and cognitive measures in children and young adults with recurrent or progressive malignant brain tumors. VII. To assess patient and/or proxy satisfaction with study participation via patient-reported outcome (PRO) measures in the context of race ethnicity and other health related social risks. VIII. To assess on therapy toxicity in the context of race, ethnicity and other health related social risks. OUTLINE: This is a dose-escalation study. Participants undergo placement of an Ommaya reservoir and receive universal donor expanded TGF-beta-imprinted NK cells (TGFBi NK cells) intratumorally over 5 minutes via Ommaya reservoir on day 1 of each cycle. Cycles repeat every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Participants also undergo magnetic resonance imaging (MRI) of the brain during screening and on study and collection of tumor-associated fluid via Ommaya reservoir on study. Participants may also undergo MRI of the spine and lumbar puncture as clinically indicated.