• Age \>18 years of age

• Disease recurrence of at least 1x1cm and a maximum of 3x3cm of enhancing tumor:

• Dose escalation portion: patients with recurrent high-grade glioma, IDH wt or IDH mutated, grade 3 or grade 4 based on imaging.

• Dose expansion portion: Recurrent, IDH wt, glioblastoma, WHO grade 4. Diagnosis has be made using the 2021 WHO Classification of Tumors of the CNS.

• The neurosurgeon must confirm (a) the tumor location (\> 1 cm from eloquent brain), (b) that the placement of infusion catheter within or through the progressive enhancing tumor is feasible and is at a safe distance to eloquent brain function. These aspects will be determined prior catheter placement on the basis of prior (screening) MRI and then at the time of catheter placement on the basis of a CT scan prior to infusion. The tip of the catheter must be placed as follows:

∙ Within the enhancing portion or in the vicinity of enhancement of target lesion (i.e., infiltrative disease)

‣ ≥ 0.5 cm from ventricles

‣ ≥ 1 cm deep into the brain

‣ ≥ 0.5 cm from the corpus callosum

• If a histological or pathological confirmation of recurrence (\< 6 weeks) is not available, a pre-infusion biopsy will be required to confirm recurrence.

• Adequate pulmonary function, with a baseline pulse oximetry of at 90% on room air.

• The subject must have received standard radiation therapy plus temozolomide and be refractory to radiation therapy plus temozolomide prior to enrollment.

• Prior to administration of MVR-C5252, the presence of recurrent tumor must be confirmed by histopathological analysis. (Distinguishing between recurrent active tumor and radiation necrosis is important to avoid delivering MVR-C5252 when there is no active disease).

• Should participants have further surgical resection at any time following their participation in the study, patients will be invited to make any biospecimens available for correlative research.

• Karnofsky Performance Status (KPS) ≥ 70%

• Labs:

∙ platelets ≥ 100,000 unsupported at initial screening, but ≥ 125,000 supported prior to biopsy/catheter insertion

‣ hemoglobin ≥ 9 gm/dL, ANC ≥ 1000/µL

‣ creatinine ≤ 1.5x upper limit of normal (ULN)

‣ total bilirubin ≤ 1.5 x ULN, AST/ALT ≤ 2.5 x ULN (subjects with known or suspected Gilbert's syndrome are excluded if total bilirubin \> 3.0 x ULN or direct bilirubin \> 1.5 x ULN)

‣ PT, aPTT ≤ 1.2 x ULN prior to biopsy (if patient is taking warfarin, INR should be obtained and be \< 2.0)

⁃ Able to undergo MRI brain with and without contrast

⁃ If the patient is a sexually active female of childbearing potential, whose partner is male, or if the patient is a sexually active male, whose partner is a female of child bearing potential, the patient must use appropriate contraceptive measures for the duration of the treatment and for 6 months afterwards. Female patients of childbearing potential must have a negative serum pregnancy test at the time of screening and within 48 hours of starting the MVR-C5252 infusion.

⁃ Signed informed consent approved by the Institutional Review Board