The primary objective of this study is to determine the safe dose range of NRG-103 in patients and to recommend the dosage for subsequent treatment, while also evaluating the preliminary efficacy and tolerability of the product.

Inclusion Criteria:

• Willing to voluntarily participate in the study, able to sign the Informed Consent Form (ICF), and willing to comply with the procedures specified in the study protocol.
• Age ≥18 years, regardless of gender.
• Participants must have a prior diagnosis of World Health Organization (WHO) Grade 3 or 4 glioma, according to the WHO (2021) classification criteria. A pathology report containing histopathological typing and necessary molecular pathology test results must be provided; this report will serve as sufficient histological documentation for study enrollment.
• Patients must have exhausted standard anti-tumor therapies or be intolerant to standard treatments (including chemoradiotherapy, targeted therapy, or immunotherapy), as evidenced by the occurrence of Grade ≥3 non-hematologic toxicities or Grade 4 hematologic toxicities. There must be definitive evidence of recurrent or progressive glioma on magnetic resonance imaging (MRI) scans (assessed according to the RANO 2.0 criteria), with no recognized effective treatment options remaining. If MRI scans are inconclusive regarding tumor recurrence or progression, surgery/biopsy is recommended; however, surgery/biopsy is not required if the investigator determines that the combination of the imaging report and clinical manifestations is sufficient to indicate tumor recurrence or progression.

Exclusion Criteria:

• Patients with known or suspected hypersensitivity to any components of the investigational medicinal product or to contrast agents.

• Patients with contraindications to magnetic resonance imaging (MRI) scanning, including but not limited to: cardiac pacemakers, epicardial pacing leads, surgical and/or aneurysm clips, shrapnel, metal prostheses, potentially magnetically active implants, metallic foreign bodies in the eye, and non-removable metal dentures.

• Patients with a history of prior gene therapy or oncolytic virus therapy.

• Patients who have participated in other clinical trials and received other investigational drugs within 28 days prior to the first administration of NRG-103.

  5, Patients who have received anti-tumor vaccines or other immunomodulatory agents (e.g., interferons, interleukin-2, thymosin, lentinan, etc.) within 4 weeks prior to enrollment. Patients who have received or are scheduled to receive live attenuated or recombinant vaccines within 4 weeks; or patients who have received or are scheduled to receive inactivated vaccines within 1 week.