Engineered immune cells take on brain cancer in early trial

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Age 18-75 years, male or female. * Good performance status: ECOG 0-2 or Karnofsky Performance Status (KPS) ≥70. * Diagnosis of relapsed/refractory primary CNS lymphoma (PCNSL) or secondary CNS lymphoma (SCNSL). * PCNSL: prior treatment with at least 2 lines and unsuitable for autologous hematopoietic stem cell transplantation; or prior treatment with at least 3 lines; or disease progression/relapse within 12 months after autologous transplantation. Participants must previously have received at least 1 line of HD-MTX-based CNS-directed therapy (intravenous dose ≥2500 mg/m²) and have documented progression, relapse, or intolerance. * SCNSL: relapse or refractory disease after at least 1 line of CNSL-directed therapy; if systemic lymphoma is also present, the systemic component must have relapsed after treatment including an anti-CD20 monoclonal antibody and an anthracycline. * Presence of measurable CNS disease (at least one enhancing lesion ≥1 cm on contrast-enhanced brain MRI, or positive CSF by flow cytometry and/or cytology). * Positive expression of CD19 and/or CD20 in tumor biopsy tissue or malignant CSF cells. Participants with prior failure of single-target CD19- or CD20-directed therapy are allowed, provided the washout period since the last treatment is at least 6 months. * Estimated life expectancy ≥12 weeks. * Adequate organ function: * Bone marrow and immune function: peripheral blood absolute CD3 count ≥50/mm³ and absolute lymphocyte count ≥0.2×10\^9/L; ANC ≥1000/μL; platelets ≥50,000/μL, without recent red blood cell or platelet transfusion. * Hepatic and renal function: creatinine clearance (Cockcroft-Gault) ≥45 mL/min; if relaxed to 30-45 mL/min, fludarabine dose must be reduced strictly; AST and ALT ≤3×ULN; total bilirubin and alkaline phosphatase ≤1.5×ULN. * Cardiopulmonary function: LVEF ≥50% (NYHA class I-II); oxygen saturation on room air \>92%. * Prior-treatment washout: anti-B-cell chemotherapy/immunotherapy stopped for at least 3 weeks; intrathecal CNS therapy stopped for at least 1 week; systemic corticosteroids (except physiologic replacement) stopped for at least 1 week; short-acting cytotoxic drugs stopped for at least 3 days. * Negative pregnancy test for women of childbearing potential; participants with partners of childbearing potential must agree to use effective contraception during treatment and for 24 months after infusion. * Voluntary participation and signed informed consent. Exclusion Criteria: * High-risk CNS status: imaging showing high-risk brain herniation or uncontrollable intracranial pressure elevation risk (large subcortical mass effect with significant cerebral edema), or severe status epilepticus or poorly controlled seizures within 14 days. * Prior severe CAR-T toxicity: prior CD19/CD20-targeted therapy (including CAR-T or bispecific antibodies) with grade IV CRS or ICANS, or grade III CRS/ICANS without full recovery after treatment. * Uncontrolled serious active infection requiring systemic intravenous therapy. * Positive virology: active hepatitis B (HBsAg positive and peripheral blood HBV DNA ≥10\^3 copies/mL); hepatitis C (HCV RNA positive); positive syphilis screening with titer ≥1:8; HIV antibody positive. * Toxicity from prior antitumor therapy not recovered to CTCAE v5.0 grade ≤2, except alopecia or fatigue. * Severe cardiovascular or respiratory disease, including myocardial infarction, unstable angina, or severe arrhythmia within the past 6 months; moderate-to-severe pulmonary arterial hypertension; or need for ventilatory support or oxygen reservoir mask assistance. * Prior history of, or concurrent, other active malignancy, except cured carcinoma in situ or basal cell skin cancer. * History of major solid organ transplantation. * Active tuberculosis at screening, or latent tuberculosis without systematic prophylaxis. * Live vaccine received within 6 weeks before lymphodepleting conditioning. * Pregnancy or breastfeeding; severe allergy to any lymphodepleting drug or any component of the CAR-T product. * Severe psychiatric disease, major depression, suicidal tendency, or any other condition that, in the investigator's judgment, makes the participant unsuitable for enrollment.