RNA-Lipid Particle (RNA-LP) Vaccines for Recurrent Adult Glioblastoma (GBM)

Inclusion Criteria:

• Age >/= 18years

• Histopathologically proven GBM using the 2021 WHO Classification of Tumors of theCNS (WHO CNS5).

• Unequivocal evidence of tumor progression as documented by brain MRI scan per RANOcriteria.

• Tumor must have a primary supratentorial component at the time of diseaseprogression.

• Patients must have received surgery and and should have completed FractionatedRadiation therapy with concurrent temozolomide as frontline treatments for primarydisease and be at least 12 weeks post chemoradiation completion.

• Patient must be at least 90 days from completion of prior radiation

• Any adverse events patient has experienced from prior therapy must have resolved to ≤ Gr. 1 according to CTCAE (NCI Common Terminology Criteria for Adverse Events) v5.0prior to enrollment

• Patient must be either weaned off steroids or weaned onto physiologic dosing at thetime of enrollment.

• Patient must be a candidate for surgery/biopsy as acceptable standard of care forsterile collection of tumor material in a manner suitable for RNA extraction,amplification, and loading of lipid particles (LPs).

• A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively andpostoperatively. Pre-op MRI must be performed within 28 days prior to studyenrollment.

• Performance Score: (KPS) ≥ 60. Participants who are unable to walk because ofparalysis, but who are up in a wheelchair, will be considered ambulatory for thepurpose of assessing the performance score.

• Bone Marrow:

• ANC (Absolute neutrophil count) ≥ 1,500µl (unsupported)

• Platelets ≥ 100/µl (unsupported for at least 3 days)

• Hemoglobin > 8 g/dL

• Renal:

• BUN ≤ 25 mg/dl

• Creatinine ≤ 1.7 mg/dl

• Hepatic

• Bilirubin ≤ 2.0 mg/dl

• ALT ≤ 5 times institutional upper limits of normal for age

• AST ≤ 5 times institutional upper limits of normal for age

• Patient must be able to give consent.

• For women of childbearing potential (WOCBP), negative serum/urine pregnancy test atenrollment.

• WOCBP must be willing to use acceptable contraceptive methods to avoid pregnancythroughout the study and for at least 24 weeks after the last dose of study drug.

• Males with female partners of childbearing potential must agree to usephysician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy)throughout the study and should avoid conceiving children for 24 weeks following thelast dose of study drug.

Exclusion Criteria:

• Patients who received prior treatment with bevacizumab.

• Known active infection (requiring treatment by antiviral or antibiotics) orimmunosuppressive disease.

• Patients with multifocal recurrent disease characterized by more than one enhancinglesion separated by noncontiguous T2/FLAIR signal abnormality. Patients withrecurrence outside of the original tumor site are eligible if there is stability atthe original site of disease.

• Patients with uncontrolled seizure disorders

• Any patients that have received any live vaccines within 30 days prior to enrollment

• Tumors with primary localization to the brainstem or spinal cord

• Severe, active co-morbidity, defined as follows:

• Unstable angina and/or congestive heart failure requiring hospitalization.

• Unstable cardiac arrhythmias, abnormalities, or transmural myocardialinfarction within the last 6 months.

• Acute bacterial or fungal infection requiring intravenous treatment at studytreatment.

• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illnessrequiring hospitalization or precluding study therapy at study treatment

• Hepatic insufficiency resulting in clinical jaundice and/or coagulationdefects.

• Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition.The need to exclude patients with AIDS from this protocol is necessary becausethe treatments involved in this protocol may be significantlyimmunosuppressive.

• Patients with autoimmune disease requiring medical management withimmunosuppressants.

• Major medical illnesses or psychiatric impairments that, in the investigator'sopinion, will prevent administration or completion of protocol therapy.

• Pregnancy or women of childbearing potential and men who are sexually activeand who are unwilling or unable to use an acceptable method of contraceptionfor the entire study period; this exclusion is necessary because the treatmentinvolved in this study may be significantly teratogenic.

• Women of childbearing potential must not be pregnant or breast-feeding.

• Participants who are receiving any other investigational agents or who have beentreated on any other therapeutic clinical protocols within 30 days prior toprojected first dose of study treatment.

• Participants who are unwilling or unable to receive treatment and undergo follow-upevaluations