CD22 Targeting CAR-T Therapy Against B Cell Hematological Malignancies

Study Overview
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Brief Summary
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CD19 expression on B cell frequently lost after CD19-targeting CAR-T therapy. In present study, we construct a CD22-targeting chimeric antigen receptor to overcome this issue.

Detailed Description
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CD19 is an ideal target with great potential for treating B-cell-derived hematological malignancies. Although the complete remission rate is as high as 93% by using CD19-targeting CAR-T technology, approximately 60% patients will have recurrent disease. Among all the recurrent patients, two thirds is revealed to loss their CD19 expression on B cell surface. For overcoming this issue, we establish a new chimeric antigen receptor containing humanized single chain antibody sequence to target CD22 molecule on B cells.

Official Title
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Application of Humanized Anti-CD22 Antibody in CAR-T Therapy of B Cell Hematological Malignancies

Conditions
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Recurrent or Refractory B Cell Malignancy

Intervention / Treatment
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* Biological: CD22 CAR-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Greater than four years of age Survival time>12 weeks B cell hematological malignancies by pathological examination Chemotherapy failure or recurrent B cell malignancy Creatinine< 2.5mg/dl Glutamic-pyruvic transaminase, glutamic oxalacetic transaminase< 3 fold of normal level Bilirubin<2.0mg/dl Karnofsky Performance Status>50% at the time of screening Adequate pulmonary, renal, hepatic, and cardiac function Fail in autologous or allogenic haemopoietic stem cell transplantation Free of leukocytes removal contraindications Voluntarily join CAR-T clinical trial Understand and sign written informed consent Exclusion Criteria: Pregnant or nursing women Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening Feasibility assessment proves that the efficiency of transduction of lymphocyte is below 10% or the lymphocyte cannot be propagated. Abnormal vital signs Highly allergic constitution or history of severe allergies, especially allergy to interleukin-2 General infection or local severe infection, or other infection that is not controlled Dysfunction in lung, heart, kidney and brain Severe autoimmune diseases Other symptoms that are not applicable for CAR-T

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD22 CAR-T<br>Enrolled patients will receive three escalating doses of autologous CAR-T. | Biological: CD22 CAR-T<br>* Autologous CAR-T cells with average 1*10^6 cells/kg body weight<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete remission rate | The B cells in peripheral blood of all enrolled patients will be monitored every week | 12 months |