Integrin β7, BCMA, CS1, CD38 and CD138 as the Single or Compound Targets for the Fourth Genenation of CAR-T Cells

According to the high expression of tumor cell-associated antigen CD138, integrin β7, CS1, CD38 and BCMA in patients with refractory/recurrent multiple myeloma, the fourth generation of CAR-T cells(simultaneously expressing IL7 and CCL19) with 10 different dual target combinations are used to minimize the tumor burden in the patient individually and precisely and improve the immunosuppressive microenvironment of the tumor , thereby effectively treating refractory/recurrent multiple myeloma .

Multiple myeloma（MM） is one of the most common malignant diseases in the blood system.There is still no cure for the disease which only control the development of the disease in various ways including proteasome inhibitors and immune regulator and hematopoietic stem cell transplantation . Combined with the advantages of multiple therapies, chimeric antigen receptor T cells (CAR-T) have gradually becoming one of the strongest and most powerful weapons against multiple myeloma.The basic principle is to use the patient's own immune cells to clear cancer cells.

MM is genetically and phenotypically heterogeneous,Antigen escape and relapse after CAR-T treatment is a global problem， so the effective treatment of refractory/relapsing multiple myeloma with CAR-T cells usually requires targeting multiple antigens. The investigators use Integrin β7(a large family of molecules that are central regulators in multicellular biology and orchestrating cell-cell and cell-extracellular matrix (ECM) adhesive interactions from embryonic development to mature tissue function), BCMA(highly expressed on malignant MM plasma cells and providing a substantial antiapoptotic signal making it an encouraging target for BCMA-directed immunotherapy),CS1(encoded by the SLAMF7 gene,a robust marker of normal plasma cells and malignant plasma),CD38(encoded by the CD38 gene and functioning in cell adhesion, signal transduction and calcium signaling) and CD138(known as syndecan 1, a surface protein expressed on most healthy and malignant plasma cells as an adhesion protein, binding collagen and fibronectin molecules located in the extracellular matrix. ) as the Single or Compound Targets for the Fourth Genenation of CAR-T Cells ,thereby effectively treating refractory/recurrent multiple myeloma .

Eligibility Criteria:
Inclusion Criteria:

1. Patients who meet the requirements voluntarily participate in the study and sign the Informed Consent Form.
2. Age is 18 to 80 years old, gender is not limited.
3. Patients with relapsed or refractory myeloma who meet the following criteria for multiple myeloma diagnostic criteria defined by the IMWG (2017): Subjects have received adequate prior treatment of at least 2 regimens; during the most recent treatment or after treatment , the disease progresses or recurs.
4. The Eastern Cancer Cooperative Group (ECOG) scores 0 to 2 (the tumor causes bone pain).
5. The expected survival period is more than 12 weeks.
6. No other malignant tumors, severe autoimmune diseases or congenital immunodeficiency, serious progressive infection, cranial nerve disorder or mental illness.

Exclusion Criteria:

1. Pregnant or lactating women.
2. Patients with uncontrollable active infections.
3. Patients with systemic steroids; recent or current use of inhaled steroids is not excluded.
4. Previously involved CAR-T cell therapies produced any uncontrolled disease.