A Phase Ib/II Clinical Trial to Evaluate the Safety and Efficacy of JL15003 Injection in Patients With Recurrent Glioblastoma (rGBM)

Inclusion Criteria:

* 1\. Age \>= 18 years of age;
* 2\. Histopathologic or radiological confirmed recurrent supratentorial GBM and measurable lesions ( \<=3 cm on contrast-enhanced MRI prior to JL15003 administration);
* 3\. Histopathology consistent with the 2021 World Health Organization (WHO) glioblastoma classification;
* 4\. Refractory or relapsed following standard-of-care therapy or intolerance to standard therapy (surgical resection followed by radiotherapy and concurrent/adjuvant temozolomide);
* 5\. Tolerable to intratumoral/intracavitary Ommaya reservoir catheter implantation;
* 6\. Karnofsky Performance Status (KPS) \>=70 and expected survival time \>= 3 months;
* 7\. Patients should have received a boost immunization with trivalent inactivated poliovirus vaccine between 1 week to 6 months prior to administration of the study drug, with a neutralizing antibody titer \>=1:8 prior to the administration;
* 8\. Able to undergo brain MRI with and without contrast;
* 9\. All subjects and their partners must have no plans for conception from screening until 90 days after the end of the observation period and must agree to use effective non-pharmacological contraceptive measures during the trial;
* 10\. Subjects voluntarily participate in the study, sign informed consent forms, have good compliance, and cooperate with follow-up.

Exclusion Criteria:

* 1\. Subjects who are allergic to any component of the investigational drug, contrast agent Maganweixian, or albumin;
* 2\. Patients with life-threatening cerebral hernia syndrome as determined by the investigator;
* 3\. Patients with combined severe or active diseases are defined as follows:
* (1) Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax \> 99.5 F/37.5 C) for more than a week;
* (2) Patients with known history of immunodeficiency (e.g., positive HIV antibody test), other acquired or congenital immunodeficiency diseases, or organ transplantation;
* (3) Patients with unstable or severe intercurrent medical conditions such as severe heart (New York Heart Association (NYHA) Class 3 or 4);
* (4) History of vascular diseases (including myocardial infarction, unstable angina pectoris, cerebrovascular disease, peripheral arterial disease, or aortic disease, etc.) within 6 months;
* (5) Uncontrolled hypertension (defined as systolic blood pressure \>= 160 mmHg or diastolic blood pressure \>= 100 mmHg on at least 2 separate occasions, despite antihypertensive medication);
* (6) Patients with active thrombosis, active bleeding, or pathological conditions posing a high risk of bleeding (e.g., coagulation disorders);
* (7) Patients with active autoimmune disease requiring systemic immunomodulatory therapy within 3 months;
* 4\. Patients with known history of agammaglobulinemia;
* 5\. Patients with tumor in the brainstem, cerebellum or spinal cord, or leptomeningeal disease; Subjects with diffuse subependymal disease;
* 6\. Head MRI suggests tumor enhancement with marginal invasion of the ventricular wall or postoperative tumor cavity connecting to the ventricle; The tumor crosses the midline;
* 7\. Patients with a history of neurological complications due to poliovirus infection;
* 8\. Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups);
* 9\. Patients with prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin;
* 10\. Patients who have received antitumor therapy (including but not limited to chemotherapy, targeted therapy, immunotherapy, TTFields, or other investigational antitumor drugs) within 4 weeks prior to the first dose of the study drug or within 5 half-lives of the previous drug (whichever is longer), and has not recovered from the toxicities (i.e., to \<= Grade 1 per CTCAE v5.0, except for alopecia; peripheral neuropathy up to Grade 2 is acceptable);
* 11\. Patients who have received radiation therapy within 12 weeks prior to the administration of the investigational drug, excluding those who have undergone radiation therapy for progressive diseases outside the radiation area;
* 12\. Patients on greater than 5 mg per day of dexamethasone or equivalent doses of other hormones (inhaled or localized use of hormones, in the absence of active autoimmune disease) within 2 weeks prior to the administration of the investigational drug;
* 13\. The laboratory tests meet the following standards:
* (1) Hemoglobin \<90g/L;
* (2) Platelet count \<100×10\^9/L;
* (3) Neutrophil count \<1.5×10\^9/L;
* (4) Creatinine \> 1.5 × upper limit of normal (ULN);
* (5) Serum total bilirubin (TBIL) \> 1.5×ULN;
* (6) AST/ALT\> 2.5×ULN;
* (7) Prothrombin and Partial Thromboplastin Times \>1.2×ULN;
* 14\. Subjects with positive syphilis antibody, or active hepatitis \[For hepatitis B: positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and HBV-DNA copy number above the upper limit of normal; for hepatitis C: positive HCV antibody and HCV RNA copy number above the upper limit of normal\];
* 15\. Subjects who have received any vaccination within 4 weeks prior to the administration of the study drug, with the exception of the inactivated poliovirus vaccine, non-live seasonal influenza vaccines, or inactivated COVID-19 vaccines, mRNA vaccines;
* 16\. Pregnancy or lactation, and a woman of childbearing potential who has a positive pregnancy test (within 7 days) prior to treatment;
* 17\. Subjects who are unsuitable for participation in this study at the Investigator's discretion.