clinical study of anti-cd56-car-t in the treatment of relapsed/refractory nk/t cell lymphoma /nk cell leukemia

Conditions: Extranodal NK T Cell Lymphoma; NK-Cell Leukemia

Summary: to evaluate the safety and efficacy of anti-cd56-car t in the treatment of relapsed refractory nk/t cell lymphoma /nk cell leukemia

extranodal nk/tcl is an aggressive disease with a poor prognosis and a 5-year survival rate of less than 50%. in the absence of effective treatment, median survival for advanced disease is only 6-12 months. a retrospective review of the international peripheral t-cell lymphoma project recently reported that the median overall survival of nk/tcl was 7.8 months, corresponding to the worst survival of all t-cell lymphoma entities. therefore, despite good results in the combination of chemoracal-chemotherapy strategies, autologous bone marrow transplantation, and l-asparagase in the treatment of recurrent cases, nk/tcl remains difficult to cure, and the need for alternative therapeutic strategies has prompted researchers to explore new molecular targets. nerve cell adhesion molecule 1 (ncam-1) -cd56 is a member of the immunoglobulin superfamily and is a biomarker of nerve cell adhesion molecule and nk cell. cd56 is highly expressed in nk/t cell lymphomas, skeletal muscle tumors, and malignancies with neurological or neuroendocrine differentiation. cd56-car t cells can kill cd56+ neuroblastoma, glioma, and sclc tumor cells in vitro coculture, and cd56r-car+t cells can inhibit tumor growth in vivo when tested against cd56+ human neuroblastoma xenogeneic and sclc models. cd56-car t cells have also been reported as a safe and effective treatment for refractory/relapsing rhabdomyosarcoma. this indicates that cd56 car has a wide clinical application prospect and strong potential therapeutic value as a new car t target. cd56 car t cells constructed by our laboratory can produce more precise killing effect on tumor cells by converting the immune checkpoint pd-1 signal. the results showed that cd56 car t cells could be prepared effectively and kill nk/ t-cell lymphoma cell line snk-6 in vitro. compared with traditional second-generation car t cells, cd56-car t cells prepared in our laboratory showed better killing effect on snk-6 cells in vitro. at present, no clinical studies on cd56 car t therapy for nk/t cell lymphoma have been reported. therefore, in this study, cd56 car t was used to treat relapsed and refractory nk/t cell lymphoma /nk cell leukemia to observe its safety and efficacy.

Eligibility criteria:
inclusion criteria: 1. patients or their legal guardians voluntarily participate and sign the informed consent; 2. male or female patients aged 18-70 years (including 18 and 70 years); 3. the patient was diagnosed as nk/t cell lymphoma /nk cell leukemia by pathology or flow cytometry, and currently has no effective treatment options, such as relapse after chemotherapy or hematopoietic stem cell transplantation; alternatively, patients voluntarily choose to administer anti-cd56-car t cells as salvage therapy. 4. the following two categories are included:(1)nk/t cell lymphoma;(2) nk cell leukemia. 5. subject: (1)there was no remission or residual lesions after treatment, and hsct (auto/allo-hsct) was not suitable; (2)relapse occurred after cr, and hsct (auto/allo-hsct) was not suitable; (3)patients with high risk factors; (4)relapse or no remission after hematopoietic stem cell transplantation or cellular immunotherapy. 6. measurable or evaluable lesions; 7. the patient's main tissues and organs function well: 1. liver function: alt/ast \< 3 times the upper limit of normal (uln) and total bilirubin ≤34.2μmol/l; 2. renal function: creatinine \< 220 μmol/l; 3. lung function: indoor oxygen saturation ≥95%; 4. cardiac function: left ventricular ejection fraction (lvef) ≥40%. 8. the patients had not received any anti-cancer treatment such as chemotherapy, radiotherapy, immunotherapy (such as immunosuppressive drugs) within the first 4 weeks of enrollment, and their previous treatment-related toxic reactions had recovered to ≤ grade 1 at the time of enrollment (except low toxicity such as hair loss); 9. the patient's peripheral shallow venous blood flow is smooth, which can meet the needs of intravenous infusion; 10. patients with ecog score ≤2 and expected survival time ≥3 months. exclusion criteria: 1. women who are pregnant (urine/blood pregnancy test positive) or breastfeeding; 2. men or women who have planned to become pregnant within the last 1 year; 3. the patients were not guaranteed to take effective contraceptive measures (condoms or contraceptives, etc.) within 1 year after enrollment; 4. patients had uncontrollable infectious diseases within 4 weeks prior to enrollment; 5. active hepatitis b/c virus; 6. hiv-infected patients; 7. suffering from a serious autoimmune disease or immunodeficiency disease; 8. the patient is allergic to antibodies, cytokines and other macromolecular biological drugs; 9. the patient had participated in other clinical trials within 6 weeks prior to enrollment; 10. systemic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones); 11. suffers from mental illness; 12. the patient has substance abuse/addiction; 13. according to the researchers' judgment, the patient had other conditions that were not suitable for inclusion.

Keywords: anti-cd56 car-t