Reform CAR structure due to safety consideration

Chimeric antigen receptor T cells (CAR-T) therapy has not yet been fully explored in solid tumors. Human epidermal growth factor receptor-2(HER2) is widely expressed in cancers. Investigators have developed anti-HER2 CAR-modified T cells and validated the efficiency targeting HER2-positive cancer in preclinical studies. This study is aimed to confirm its adverse effects including cytokine storm response and any other adverse effects. In addition, CAR-T cells persistence, tumor elimination and disease status after treatment will be evaluated.

Inclusion Criteria:

1. Relapsed or refractory HER2 positive cancer.

2. KPS>60.

3. Life expectancy>3 months.

4. Gender unlimited, age from 18 years to 80 years.

5. Assessable lesions with a minimum size of 10mm by CT scan or MRI.

6. Acceptable organ function

   Hematology:

   • Absolute neutrophil count greater than 800/mm^3 without the support of filgrastim.
   • White blood cell (WBC) (> 2000/mm^3).
   • Platelet count greater than 50,000/mm^3.
   • Hemoglobin greater than 9.0 g/dl.

   Chemistry:

   • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 3 times the upper limit of normal (patients without liver metastasis) or 6 times the upper limit of normal (patients with liver metastasis).
   • Serum creatinine less or equal to 3 times the upper limit of normal
   • Total bilirubin less than or equal to 3 times the upper limit of normal.

7. No other serious diseases(autoimmune disease, immunodeficiency etc.).

8. Adequate cardiac function(LVEF≥40%).

9. No other tumors.

10. Patients volunteer to participate in the research.

Exclusion Criteria:

1. Allergic to cytokines.
2. Uncontrolled active infection.
3. Acute or chronic GVHD.
4. MODS.
5. Treated with T cell inhibitor.
6. HIV affected.
7. Other situations improper for the research.