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

Wei Guan

Status and phase

Not yet enrolling

Early Phase 1

Conditions

Advanced Renal Cell Carcinoma

Treatments

Biological: CAR-T(CD70)

Study type

Interventional

Funder types

Other

Identifiers

NCT07113977

TJ-IRB202502144

Details and patient eligibility

About

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.

Enrollment

30 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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.