This is a single-arm study to evaluate the efficacy and safety of CD207 targeted CAR-T cell therapy in relapsed and refractory langerhans cell histiocytosis.

There are limited options for treatment of r/r langerhans cell histiocytosis. CD207 is expressed on the membrane surface of langerhans cells，and it is an ideal target for CAR-T. In this study, investigators will evaluate the safety and efficacy of CD207 targeted CAR- T cell therapy in patients with r/r langerhans cell histiocytosis. The primary goal is safety and efficiency assessment, including incidence and severity of adverse events and overall response rate.

Inclusion Criteria:

1. Relapsed or refractory langerhans cell histiocytosis, defined as: 1) any relapse during standard chemotherapy; 2) not responding to standard chemotherapy; 3) not achieving CR after first cycle of second-line chemotherapy for relapsed langerhans cell histiocytosis;
2. 3-65 years old;
3. Expected survival time ≥ 3 months;
4. ECOG performance status of 0 or 1 (age ≥ 16 years) or Karnofsky performance status> 80 (age < 16 years) ;
5. With single or venous blood collection standards, and no other cell collection contraindications;
6. WBC ≥ 2.5×10^9/L ，LY ≥ 0.7×10^9/L，LY% ≥15%;
7. Serum creatinine ≤ 2.0 mg/dl;
8. ALT/AST ≤ 2.5 x ULN;
9. Total bilirubin ≤ 2.0 mg/dl;
10. PT:INR<1.7, or PT is within 4s of the normal value;
11. Ability and willingness to adhere to the study visit schedule and all protocol requirements.

Exclusion Criteria:

1. Transduced CAR+ T lymphocytes<5%, or expansion <5 folds after stimulation with anti CD3/anti CD28 beads;
2. Pregnant or breasting-feeding women;
3. Active hepatitis B or hepatitis C infection;
4. Patients with HIV infection;
5. Uncontrolled active infection;
6. Use of systemic corticosteroid therapy;
7. Have received gene therapy, or any other CAR-T treatment;
8. Allergic to immunotherapy and related drugs;
9. History of heart disease requiring treatment, or poorly controlled hypertension;
10. Preceding and/or ongoing active ulcer or gastrointestinal bleeding;
11. Have received allogeneic hematopoietic stem cell transplantation, or eligible for allogeneic hematopoietic stem cell transplantation;
12. Severe central nervous system involvement;
13. Severe lung involvement;
14. Hyponatremia (serum sodium<125mmol/L);
15. Hypokalemia (Serum kalium<3.5mmol/L);
16. Those who need long-term anticoagulation treatment (warfarin or heparin);
17. Those who need long-term antiplatelet treatment (aspirin, dose>300mg/d; clopidogrel, dose>75mg/d);
18. Radiation therapy within 4 weeks prior to registration;
19. Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, congestive heart failure, unstable angina, cardiac arrhythmias, mental illness, and other diseases that in the opinion of the investigator would pose an unacceptable risk to the subject;
20. Have a history of severe allergy;
21. Current enrollment in another study;
22. Patients with other contraindications considered unsuitable for participation in this study (according to investigator's judgement).