This is a single-arm, open-label, dose-escalation study to evaluate the safety, tolerability, cellular kinetics and initial efficacy of CAR-T cell therapy targeting GPRC5D in multiple myeloma subjects who have failed the standard treatments.

Inclusion Criteria:

1. The subject can understand and have the ability to sign an informed consent form;

2. Male or female subjects, aged 18-75 years;

3. The expected survival period is not less than 12 weeks;

4. ECOG score ≤ 2 ;

5. Diagnosed as multiple myeloma according to the IMWG standard in 2018;

6. The expression of GPRC5D in bone marrow plasma cells is more than 20%, or it is positive in tumor tissue by immunohistochemistry. One of the following criteria must be detected:

   1. If IgG type MM, serum M protein ≥10g/L; if IgA, IgD, IgE or IgM type MM, serum M protein ≥5g/L;
   2. Or urine M protein level ≥200mg/24h;
   3. Or light chain type MM, serum free light chain (sFLC) ≥ 100mg / L and K/ λ FLC ratio is abnormal;
   4. Or there are extramedullary lesions;

7. Subjects who have received at least 3 different mechanism drugs (including chemotherapy, protease inhibitors, immunosuppressive agents, etc.) have failed treatments, or have progressed or recurred during the last treatment or within 6 months after the end of treatment ;

8. Lung function is normal, and oxygen saturation is greater than 92%;

9. No heart disease or coronary heart disease, echocardiogram showed normal diastolic function, left ventricular ejection fraction (LVEF) ≥50%, and no serious arrhythmia;

10. Liver function: TBIL<3×ULN, AST<2.5×ULN, ALT<2.5ULN;

11. Renal function: creatinine clearance rate (estimated by Cockcroft Gault formula) ≥ 30 mL/min;

12. The blood routine meets the following standards:

    1. Lymphocyte count>0.5×10e9/L;
    2. Neutrophils ≥1.0×10e9/L;
    3. Hemoglobin ≥80g/L;
    4. Platelet ≥75×10e9/L

13. From the use of study drug to 2 years after treatment, male subjects or female subjects of childbearing age must agree and be able to take effective contraceptive measures.

Exclusion Criteria:

1. Pregnant or breastfeeding;
2. HBsAg or HBcAb are positive, and the quantitative detection of HBV DNA in peripheral blood is more than 100 copies / L; HCV antibody and HCV RNA in peripheral blood are positive; HIV antibody positive; Syphilis antibody is positive in the first screening;
3. Any unstable systemic disease: including but not limited to unstable angina, cerebrovascular accident or transient cerebral ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure (New York Heart Association [NYHA] classification ≥ grade III), severe arrhythmia with poor drug control, liver, kidney or metabolic diseases;
4. Had hypersensitivity or intolerance to any drug used in this study;
5. Patients who received anti-cancer chemotherapy or other medications within 2 weeks before screening;
6. Uncontrolled malignant tumors except MM, excluding malignant tumors that received radical treatment and no active disease was found within 3 years before enrollment;
7. Clinically significant central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, psychosis, active central nervous system involvement or cancerous meningitis;
8. In the past two years, autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) caused damage to terminal organs, or required systemic application of immunosuppressive or other drugs;
9. Severe active viral, bacterial or uncontrolled systemic fungal infections; Hereditary bleeding / coagulation diseases, history of non traumatic bleeding or thromboembolism, other diseases that may increase the risk of bleeding, etc;
10. Patients who received autologous hematopoietic stem cell transplantation (ASCT) within 8 weeks before screening, or who plan to undergo ASCT during the study period;
11. Patients received allogeneic stem cell therapy;
12. Any unsuitable to participate in this trial judged by the investigator.