Clinical Study of a Novel Humanized CD70-Targeted CAR-T Cell Incorporating TLR2 for Advanced Renal Cell Carcinoma Therapy

Clinical Study of a Novel Humanized CD70-Targeted CAR-T Cell Incorporating TLR2 for Advanced Renal Cell Carcinoma Therapy

In this clinical study, participants with advanced renal cell carcinoma will receive a novel humanized CD70-targeted CAR-T-cell product that incorporates the TLR2 co-stimulatory domain. Peripheral blood mononuclear cells will be collected from each subject, genetically modified to express the CAR construct, and expanded ex vivo; after passing multiple quality-control assays, the CAR-T cells will be infused at the pre-specified dose. Post-infusion, the efficacy and safety of CD70-directed CAR-T-cell therapy will be systematically evaluated using clinical symptom assessments, quality-of-life questionnaires, biomarker analyses, laboratory tests, imaging studies, adverse-event monitoring, and long-term follow-up.

Inclusion Criteria:

• 1. Voluntary participation with written informed consent provided by the patient or legally authorized representative;

• 2.Age 18-75 years (inclusive) at the time of consent, regardless of sex;

• 3.Advanced-stage renal cell carcinoma (RCC) with no curative treatment options, who have received ≥1 prior line of therapy and meet one or more of the following:

  1. Recurrence after first-line or later-line treatment(s).
  2. Progression or persistent progression following prior therapy;

• 4.Histopathologically confirmed advanced RCC per WHO 2016 classification, with at least one measurable lesion evaluable by CT or MRI;

• 5.CD70 positivity in tumor tissue confirmed by immunohistochemistry (IHC);

• 6.Adequate organ function: Hepatic: ALT/AST <3× ULN and total bilirubin ≤34.2 μmol/L. Renal: Creatinine clearance (Cockcroft-Gault) ≥60 mL/min. Pulmonary: Oxygen saturation ≥95% with no active pulmonary infection. Cardiac: LVEF ≥50%, no significant pericardial effusion, and no clinically relevant ECG abnormalities;

• 7.Contraception: Women of childbearing potential must have a negative pregnancy test (urine/serum) at screening and agree to use effective contraception for ≥1 year post-infusion.

Men with partners of childbearing potential must use barrier contraception for ≥1 year post-infusion;

• 8.Performance status: ECOG score 0-3;
• 9.Life expectancy >3 months;
• 10.Willingness to comply with leukapheresis, medical assessments, and follow-up visits.

Exclusion Criteria:

• 1.Pregnant or lactating women;
• 2.Uncontrolled fungal, bacterial, Treponema pallidum, viral, or other infections;
• 3.Active hepatitis: HBV DNA >500 IU/mL. Positive HCV RNA (confirmed by repeat testing);
• 4.HIV infection, known acquired immunodeficiency syndrome (AIDS), or syphilis infection;
• 5.Prior gene therapy of any form;
• 6.History of severe allergic reactions to biologics (including antibiotics), antibodies, cytokines, or other macromolecular agents;
• 7.Clinically significant CNS disorders: epilepsy, paresis, aphasia, stroke, severe traumatic brain injury, dementia, Parkinson's disease, cerebellar disorders, organic brain syndrome;
• 8.Uncontrolled psychiatric illness;
• 9.Substance abuse/addiction;
• 10.Prohibited medications/treatments: Corticosteroids: ≥2 mg/kg prednisone (or equivalent >20 mg/day) within 2 weeks before leukapheresis.

Chemo/radiotherapy: Anti-tumor radiotherapy or salvage chemotherapy within 3 weeks before leukapheresis.

Immunosuppressants: Use within 4 weeks before leukapheresis. Other trials/major surgery: Participation in another clinical trial or major non-diagnostic surgery within 4 weeks before leukapheresis.

Specific agents: Alemtuzumab within 6 months, or clofarabine/cladribine within 3 months before leukapheresis.