Claudin18.2-redirected Chimeric Antigen Receptor T Cells With Co-expression of Cytokines in Solid Tumors

Inclusion Criteria:

1. Aged 18 to 75 years, male or female;
2. Estimated life expectancy \> 12 weeks;
3. Pathologically/histologically confirmed diagnosis of advanced G/GEJ adenocarcinoma or pancreatic cancer or other digestive system malignancies G/GEJA: refractory to or intolerable of at least 2 prior lines of treatment; HER2+ subjects must be refractory or intolerable of anti-HER2 treatment PC: refractory to or intolerable of at least 1 prior line of treatment;
4. Positive expression of CLDN18.2 in tumor tissue specimens;
5. According to the RECIST 1.1, there is measurable or unmeasurable tumor lesions;
6. ECOG physical status score 0 \~ 1 at screening, within 24 hours prior to apheresis;
7. Sufficient venous access for leukapheresis (central venous catheter)
8. Subjects should have adequate organ functions before screening :
9. Women of childbearing age (WOCB) be willing to use effective and reliable method of contraception (annual failure\<1%) for at least 1 year after last infusion, and must refrain from donating sperms/eggs
10. Men who have actively sexual intercourse with women with child-bearing potential, must agree to use barrier-based contraception if they have no vasectomy. Moreover, all men are absolutely forbidden to donate sperm within 1 year after receiving the last infusion.

Exclusion Criteria:

1. High risks that may cause bleeding or perforation;
2. CNS metastasis, with or without related symptoms;
3. The presence of extensive lung metastases, or extensive liver metastases, or extensive bone metastases
4. History or current unstable or active digestive ulcers, gastrointestinal (GI) bleeding, GI obstruction;
5. Anti-tumor treatment for the investigational disease; treatment with anti-PD-1/PD-L1, anti-CTLA4, and any other immunotherapy or investigational therapy；
6. Prior treatment with any genetically modified cell therapy;
7. Treatment with systemic corticosteroids within 7 days prior to leukapheresis;
8. Prior solid organ transplantation, or allogeneic stem cell, or in the waiting list for organ transplantation;
9. Major surgical procedure or serious wound within 4 weeks prior to leukapheresis, or anticipation of need for a major surgical procedure during the study;
10. Positive serological tests of HIV, syphilis or HCV (subjects with positive HCV antibody but are negative for HCV RNA are eligible);
11. Any active or severe infection, incl. but not limited to active tuberculosis, HBV infection, etc.;
12. Active autoimmune disease;
13. Uncontrolled significant cardiovascular disease, pulmonary disease or CNS disease
14. History of malignancy other than investigational diseases within 3 years, with the exception of malignancies with a negligible risk of metastasis or death;
15. Pregnancy or lactating women;
16. History of allergic anaphylactic reactions to immunotherapy, and/or tocilizumab, cyclophosphamide, fludarabine or nab-paclitaxel, and/or CT048 components, or other history of severe allergic anaphylactic reactions ；
17. Blood oxygen saturation ≤95% before leukapheresis;
18. AEs from previous treatment that have not recovered to CTCAE ≤ grade 1, excluding hair loss, pigmentation, and other tolerable events and laboratory abnormalities permitted by the protocol;