RNA Lipid Particles Targeting Pediatric Recurrent Intracranial Malignancies and Other systEmic Solid Tumors

Inclusion Criteria: Patients with recurrent or progressive pediatric high-grade glioma (pHGG) Patients must be age 3-25 years Diagnosis: Patients must have had a prior histologically-diagnosed pHGG(including but not limited to: Astrocytoma WHO Grade 3 or 4 and Glioblastoma WHO Grade 4 by histopathology or molecular studies, per 2021 WHO Classification of Tumors of the CNS57, WHO CNS5). * Patients with M+ disease without gliomatosis cerebri (see definition under exclusion criteria) ARE eligible. * Recurrent pHGG involving the midline structures other than those intrinsically located within the pons ARE eligible. * Patients with mismatch repair deficient (MMRD) tumors refractory to immune checkpoint inhibitors ARE eligible. Patients must have recurred or progressed after receiving surgery/biopsy and radiation therapy as frontline standard-of-care treatments in primary disease. Patients must have MRI evidence of probable recurrent pHGG. Patients must be clinically eligible for standard-of-care surgical resection/biopsy and sterile collection of tumor material in a manner suitable for RNA extraction, amplification, and loading of lipid particles. Performance Level Karnofsky ≥ 60% for patients ≥ 16 years of age and Lansky ≥ 60% for patients ≤ 16 years of age * Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * Participants with post-surgical neurological deficits should have deficits that are stable for a minimum of 2 week prior to enrollment. Prior Therapy Patients must have recovered from all acute toxic effects of all prior anti-cancer therapy (all adverse events must have improved to grade 1 or better): * Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: ≥ 21 days after the last dose of myelosuppressive chemotherapy. If questions, the agent and duration can be discussed with the study chair. * Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or ANC counts): ≥ 14 days after the last dose of agent. If questions, the agent and duration can be discussed with the study chair. * Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1. * Corticosteroids: All systemically administered corticosteroids must be stable or decreasing for ≥ 1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg/m2/day. Corticosteroid physiologic replacement therapy for management of pituitary/adrenal axis insufficiency and/or topical administration (e.g. inhaled or dermatologic) is allowed. * Hematopoietic growth factors: ≥14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. * Interleukins, Interferons, and Cytokines (other than hematopoietic growth factors): ≥ 21 days after the completion of interleukins, interferon, or cytokines. * Stem cell infusions (with or without TBI): * Autologous stem cell infusion including boost infusion: ≥ 30 days. * Cellular Therapy: ≥ 42 days after the completion of any type of cellular therapy (e.g., modified T cells, NK cells, dendritic cells, etc.) * XRT/External Beam Irradiation, including Protons: ≥ 90 days after local XRT unless recurrence is a new enhancement on MRI outside the radiation treatment field; ≥ 150 days after TBI, craniospinal XRT or if radiation to ≥ 50% of the pelvis. * Radiopharmaceutical therapy (e.g., radiolabeled antibody): ≥ 42 days after systematically administered radiopharmaceutical therapy. * Other therapeutic clinical trials: ≥ 14 days after last dose of investigational agent, unless otherwise defined above. * Prior use of RNA-LP therapy: Patients must not have received prior exposure to pp65-directed therapy or any RNA-LP therapy. Organ Function Requirements Adequate bone marrow function as defined as: * Absolute neutrophil count (ANC) ≥ 1,000/µl * Platelets ≥ 100,000/µl (transfusion-independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) * Hemoglobin ≥ 8 g/dL (transfusion-independent, defined as not receiving packed red blood cell transfusions for at least 7 days prior to enrollment) Adequate renal function as defined as: * A creatinine based on age/gender * Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 Adequate liver function as defined as: * Total bilirubin ≤ 3x institutional upper limits of normal for age * ALT ≤ 5x institutional upper limits of normal for age * AST ≤ 5x institutional upper limits of normal for age Adequate pulmonary function defined as baseline pulse oximetry of at least 92% on room air. All patients must be willing to take an antiepileptic medication such as levetiracetam for the duration of RNA-LP vaccinations. Contraception * Women of childbearing potential must agree to use of at least 2 forms of acceptable contraceptive methods or abstinence to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug. * Men with female partners of childbearing potential must agree to use of at least 2 forms of acceptable contraceptive methods or abstinence throughout the study and should avoid conceiving children for at least 24 weeks following the last dose of study drug. All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent/assent document. Inclusion Criteria: Patients with osteosarcoma (OSA) Age: Patients must be age 3-39 years. Diagnosis * For Arms 1 and 2: Patients must be clinically eligible for standard-of-care surgical resection of suspected OSA recurrence with pulmonary-only metastases. * For Arm 3: Patients must undergo standard-of-care biopsy of suspected or known recurrent, unresectable OSA. Disease Status * For Arm 1: Patients must be eligible for single-sided thoracotomy for planned surgical resection of all OSA pulmonary metastases. * For Arm 2: Patients must be eligible for staged two-sided thoracotomies for planned surgical resection of all OSA pulmonary metastases. * For Arm 3: Patients must have unresectable OSA. Patients must have sufficient disease on diagnostic contrast-enhanced MRI wherein surgical biopsy is feasible. Patients must have sterile collection of tumor material in a manner suitable for RNA extraction, amplification, and loading of lipid particles. Performance Level: Karnofsky ≥ 60% for patients \> 16 years of age and Lansky ≥ 60% for patients \< 16 years of age. * NOTE: Participants who are unable to walk because of amputation, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. Prior Therapy: Patients must have recovered from all acute toxic effects of all prior anti-cancer therapy (all adverse events must have improved to grade 1 or better): Prior Therapy: Patients must have recovered from all acute toxic effects of all prior anti-cancer therapy (all adverse events must have improved to grade 1 or better): 1. Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: ≥ 14 days after the last dose of myelosuppressive chemotherapy. If questions, the agent and duration can be discussed with the study chair. 2. Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or ANC counts): ≥ 7 days after the last dose of agent. If questions, the agent and duration can be discussed with the study chair. 3. Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1. 4. Corticosteroids: All systemically administered corticosteroids must be stable or decreasing for ≥ 1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg/m2/day. Corticosteroid physiologic replacement therapy for management of pituitary/adrenal axis insufficiency and/or topical administration (e.g. inhaled or dermatologic) is allowed. 5. Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥ 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. 6. Interleukins, Interferons, and Cytokines (other than hematopoietic growth factors): ≥ 21 days after the completion of interleukins, interferon, or cytokines. 7. Stem cell infusions (with or without TBI): Autologous stem cell infusion including boost infusion: ≥ 30 days. 8. Cellular Therapy: ≥ 42 days after the completion of any type of cellular therapy (e.g., modified T cells, NK cells, dendritic cells, etc.). 9. XRT/External Beam Irradiation, including Protons: ≥ 90 days after local XRT unless recurrence is a new enhancement on MRI outside the radiation treatment field; ≥ 150 days after TBI or if radiation to ≥ 50% of the pelvis; ≥ 42 days if other substantial BM radiation. 10. Radiopharmaceutical therapy (e.g., radiolabeled antibody): ≥ 42 days after systematically administered radiopharmaceutical therapy. 11. Other therapeutic clinical trials: ≥ 14 days after last dose of investigational agent, unless otherwise defined above 12. Prior use of RNA-LP therapy: Patients must not have received prior exposure to pp65-directed therapy or any RNA-LP therapy. Organ Function Requirements Adequate bone marrow function as defined as: * Absolute neutrophil count (ANC) ≥ 1,000/µl * Platelets ≥ 100,000/µl (transfusion-independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) * Hemoglobin ≥ 8 g/dL (transfusion-independent, defined as not receiving packed red blood cell transfusions for at least 7 days prior to enrollment) Adequate renal function as defined as: * A creatinine based on age/gender * Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2 Adequate liver function as defined as: * Total bilirubin ≤ 3x institutional upper limits of normal for age * ALT ≤ 5x institutional upper limits of normal for age * AST ≤ 5x institutional upper limits of normal for age Adequate pulmonary function defined as baseline pulse oximetry of at least 92% on room air. Contraception * Women of childbearing potential must agree to use of at least 2 forms of acceptable contraceptive methods or abstinence to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug. * Men with female partners of childbearing potential must agree to use of at least 2 forms of acceptable contraceptive methods or abstinence throughout the study and should avoid conceiving children for at least 24 weeks following the last dose of study drug. All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent/assent document. Exclusion Criteria for all Strata Diagnosis * Diffuse intrinsic pontine glioma * Gliomatosis cerebri - clear tumor involvement of multiple areas (\>3 lobes), OR presence of clinical and/or radiographic evidence of impending herniation or spinal cord compression. NOTE: review by Study Chairs is recommended Patients who are receiving any other investigational agents. Pregnancy or Breastfeeding o Pregnant or breastfeeding women will not be entered on this study because there is no available information regarding human fetal or teratogenic toxicities. Females of childbearing potential must have negative serum or urine pregnancy test within 72 hours prior to starting protocol therapy. Severe, active co-morbidity, including, but not limited to: * Known active immunosuppressive disease. * Unstable angina and/or congestive heart failure requiring hospitalization. * Unstable cardiac arrhythmias, abnormalities, or transmural myocardial infarction within the last 6 months. * Uncontrolled infection * Chronic Obstructive Pulmonary Disease (COPD) exacerbation or other known respiratory illness requiring hospitalization or precluding study therapy * Hepatic insufficiency resulting in clinical jaundice and/or clinically significant coagulation defects. * Patients with autoimmune disease requiring medical management with immunosuppressants. * Prior history of brachial neuritis or Guillain-Barre syndrome. * Uncontrolled seizure disorder * Major medical illnesses or psychiatric impairments that, in the investigators' opinions, will prevent administration or completion of protocol therapy. History of myocarditis Receipt of any live vaccine within 30 days prior to day 1 of treatment. Patients who have received an allogeneic (non-autologous) bone marrow or stem cell transplant, or any allogeneic stem cell infusion including DLI or boost infusion. Participants who are unwilling or unable to receive treatment and undergo follow-up evaluations, or who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.