Key Inclusion Criteria:
* Age ≥ 18 years.
* Confirmed recurrent malignant high-grade (WHO grade 3-4) glioma who have received standard therapy and no available treatment.
* Measurable lesions exist in accordance with RANO criteria.
* Sufficient space for ≥1 mL drug infused into tumor cavity post resection.
* Ommaya reservoir has been placed in the operation area, and drug administration conditions are available.
* Karnofsky Performance Status (KPS) ≥ 60%
* Life expectancy \> 12 weeks.
* No severe hematological, cardiovascular, liver or kidney diseases.
* If the patient is a sexually active female of childbearing potential or if the patient is a sexually active male whose partner is a female of childbearing 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 within 7 days of before the C5252 infusion.
* Capable of understanding and complying with protocol requirements.
Key Exclusion Criteria:
* Inability to undergo MRI examination for any reason.
* Active hemorrhage observed before enrollment.
* Imaging test: a. lesion located in non-cerebral regions; b. there are other lesions outside target tumor cavity; c. extra-cranial metastasis.
* Tumor lesion locates in ventricular system or there is a clear perforation between the tumor cavity and the ventricle after tumor resection.
* History of encephalitis, multiple sclerosis or other central nervous system infections
* Treated with steroid hormones and/or more than 5 mg dexamethasone per day or other immunosuppressive drugs for systemic treatment within 4 weeks.
* Persistent or active infection, and cannot be controlled by treatment.
* Subjects with bleeding tendency or need to take anticoagulant drugs, antiplatelet drugs or non-steroidal anti-inflammatory drugs (NSAIDs) and are unable to discontinue.
* Uncontrolled disease, including but not limited to symptomatic congestive heart failure, unstable angina pectoris.
* Other malignant tumor within 5 years.
* Patients who require an attenuated or live vaccine within 28 days prior to the first trial drug administration and during the study treatment period.
* In the period of recurrent herpes simplex virus infection, with corresponding clinical manifestations.
* Systemic use (other than topical) of anti-HSV drugs
* Prior treatment with any oncolytic virus, cell therapy or gene therapy.
* Participants have a history of splenectomy, organ transplantation, bone marrow transplantation or stem cell transplantation
* Prior antitumor treatment with intracranial implants, such as Carmustine.
* Previous history of allergic reactions to similar biological components such as HSV-1, IL-12 or anti-PD-1 antibodies, or with known allergic reactions to any component of the C5252 prescription, including glycerol.
* Developed ≥Grade 3 irAE during previous immunotherapy
* History of frequent drug use (including "recreational use") or drug abuse (including alcohol abuse) within one year prior to signing the informed consent form.
* Other situation that PI consider subjects not appropriate to participate in the study.
