A Clinical Trial Targeting CEA Chimeric Antigen Receptor T (CAR-T) for CEA Positive Advanced Malignant Solid Tumors

Inclusion Criteria:

1. Age ≥18 years old, male or female;
2. Patients with advanced malignant solid tumors confirmed by histology or pathology,including colorectal cancer, esophageal cancer, gastric cancer, pancreatic cancer,non-small cell lung cancer, breast cancer, and cholangiocarcinoma;
3. Progression or intolerance occurs after receiving systematic standard therapyaccording to guidelines,(systemic therapy including but not limited to systemicchemotherapy, molecular targeting, etc.) and is not suitable for surgery or localtherapy (including ablative therapy, interventional therapy, and radiation therapy),among which colorectal cancer needs to receive at least third-line therapy failure orintolerance or inapplicability. Esophageal, gastric, non-small cell lung, breast, andcholangiocarcinoma require at least second-line treatment failure or intolerance orinadequacy, and pancreatic cancer require at least first-line treatment failure orintolerance or inadequacy:
4. Advanced colorectal cancer: progression or intolerance or inadequacy afterthird-line standard therapy including cetuximab ± Irinotecan/regorafenib /fruquintinib/trifluridine；
5. Advanced or metastatic esophageal cancer/esophagogastric junction cancer:patients with esophageal cancer who progress or are intolerant or inapplicableafter second-line therapy including PD-1 MAB /PD-L1 mab; Patients withesophagogastric junction cancer progressed or were intolerant or inapplicableafter second-line therapy including taxane or irinotecan or PD-1 /PD-L1monoclonal antibody; For HER-2 positive patients, trastuzumab containing systemtherapy should fail or be intolerable or not applicable;
6. Advanced/metastatic gastric cancer: the combination of PD-1 MAB /PD-L1 MAB andchemotherapy has been developed or is not tolerated or suitable; For HER-2positive patients, systemic treatment containing trastuzumab should fail or beintolerable or inapplicable.
7. Patients with advanced, metastatic, or recurrent non-small cell lung cancer whohave received systemic treatment progression or intolerance, including: Patientswith positive driver genes (EGFR, ALK, ROS1, BRAF, NTRK, MET, RET) should receivetargeted therapy failure or drug resistance (squamous cell carcinoma does notrequire driver gene testing). In addition, patients with EGFR-positive drivergene who are resistant to first-line EGFR-Tkis and who are positive for EGFRT790M mutations need to be treated with third-generation EGFR-TKI (such asOsimertinib, almonertinib, or furmonertinib) after failure or resistance. Forpatients with positive ALK fusion and drug resistance after first-line crizotinibtreatment, second-line treatment with ceritinib or alectinib should fail or beresistant; Patients with PD-L1 expression (PD-L1 TPS≥1%) should undergo immunecheckpoint inhibitor treatment failure or intolerance; In patients with negativedriver genes, the disease progresses or becomes intolerable after chemotherapywith platinum-containing regiments-such as Camrelizumab, Pembrolizumab,Tislelizumab, Sintilimab or Atezolizumab combined with pemetrexed
8. Advanced, metastatic breast cancer: HER-2 positive patients need to have receivedanti-HER-2 therapy, hormone receptor positive patients need to receive endocrinetherapy and other standard treatments have failed or are intolerable or notapplicable, and rescue chemotherapy for those who have failed/are intolerable ortriple-negative breast cancer (including: Gemcitabine + cisplatin/carboplatin,albumin paclitaxel/other taxoid drugs + cisplatin/carboplatin) fail or are nottolerated or suitable;
9. Locally advanced or metastatic pancreatic cancer: advanced or intolerant orinappropriate after at least first-line treatment, including: Gemcitabine +albumin-bound paclitaxel/cisplatin/erlotinib/capecitabine/tegafur/Nimotuzumab, orFOLFIRINOX (oxaliplatin + irinotecan +LV+5-FU), or mFOLFIRINOX (oxaliplatin +irinotecan + calcium folinate +5-FU);
10. Advanced cholangiocarcinoma: progression or intolerance or inapplicability afterat least second-line therapy (mFOLFOX); Remarks: Chemotherapy failure is definedas disease progression or intolerable toxicity during treatment or within 3months after the last dose; If patients cannot receive the above treatment foreconomic reasons, those whose benefits outweigh the risks of inclusion in thestudy can be enrolled.
11. Subjects with positive CEA (IHC score 3+) in tumor tissue samples (paraffin sectionsor fresh tissue specimens or puncture biopsy samples) within 3 months beforescreening; If the immunohistochemical results of the tumor samples are more than 3months from the time of screening, the patient needs to re-biopsy; If the tumorspecimens are not available or the amount is too small for immunohistochemicaldetection of CEA, the CEA positive can be confirmed by re-staining of previous tissuespecimens, and the peripheral blood serum CEA≥2.0×ULN can be included in the group.
12. Have at least one evaluable target lesion according to RECIST 1.1 criteria;
13. Colorectal cancer, esophageal cancer, non-small cell lung cancer, breast cancer,stomach cancer, cholangiocarcinoma ECOG 0 ~ 1 score, pancreatic cancer ECOG 0 ~ 2score;
14. Expected survival time is more than 12 weeks;
15. No serious mental disorders;
16. Unless otherwise stated, the subject's vital organ functions shall meet the followingconditions:
17. Blood routine: white blood cells > 3.5×109/L, neutrophils > 1.8×109/L,lymphocytes > 0.5 ×109/L, platelet > 80×109/L, hemoglobin > 90g/L;
18. Cardiac function: Echocardiography indicated cardiac ejection fraction ≥50%, andno obvious abnormality was found in electrocardiogram;
19. Renal function: serum creatinine ≤2.0×ULN;
20. Liver function: ALT and AST≤3.0×ULN (patients with liver tumor infiltration canbe relaxed to ≤5.0 ×ULN);
21. Total bilirubin ≤2.0×ULN (Gilbert syndrome ≤3.0×ULN; The patients with livertumor infiltration can be enlarged to ≤5.0×ULN);
22. Blood oxygen saturation in non-oxygen state > 92%.
23. Have the criteria for simple or intravenous blood collection, and no othercontraindications for cell collection;
24. The subject agrees to use a reliable and effective method of contraception (excludingsafe period contraception) for 1 year from signing the informed consent to receivingthe C-13-60 cell infusion. Including but not limited to: abstinence, can inhibitovulation implantable progesterone contraceptive; Intrauterine device (IUD);Intrauterine hormone release system; Spousal vasectomy; Combined hormonalcontraceptives (oral, vaginal, and transdermal) that inhibit ovulation; Progesteronecontraceptives (oral or injectable) that inhibit ovulation; Male subjects who have sexwith fertile women must consent to the use of a barrier method of contraception (e.g.,condom plus spermicidal foam/gel/film/emulsion/suppository). At the same time, thesubject should promise not to donate eggs (egg cells, oocytes) or sperm for assistedreproduction within 1 year after the cell infusion.
25. The patient or his/her guardian agrees to participate in the clinical trial and signsthe ICF, indicating that he/she understands the purpose and procedure of the clinicaltrial and is willing to participate in the study.

Exclusion Criteria:

1. People who have received CAR-T therapy or other gene-modified cell therapy;
2. Patients with BMS with clinical symptoms or lesions located in key parts of the brainat the time of screening, patients with BMS without clinical symptoms or lesionslocated in non-critical parts of the brain should be evaluated by researchers orspecialists to gain more than the risk.
3. Received any of the following medications or treatments before screening:
4. Received other investigational drugs or treatments that are not on the marketwithin 4 weeks prior to screening;
5. Received live attenuated vaccine within 4 weeks prior to screening;
6. Received radioactive iodine-125 particle implantation within 8 weeks prior toscreening;
7. Received the following drugs or treatments before apheresis:
8. received the equivalent of &gt within 2 weeks prior to apheresis; 10mg/ day ofprednisone for systemic steroids, except inhaled steroids;
9. Received anti-PD-1 / PD-L1 monoclonal antibody treatment within 4 weeks beforeapheresis; Received chemotherapy, targeted therapy, or other investigationalagents within 2 weeks of preapheresis or at least 5 drug half-lives (whichever isshorter);
10. There is an active or uncontrolled infection that requires systemic treatment within 1week prior to screening;
11. Subjects with intestinal obstruction, active gastrointestinal bleeding, history ofmassive gastrointestinal bleeding within 3 months, severe gastroduodenal ulcer, severeulcerative colitis and other severe intestinal inflammation;
12. History of severe respiratory disease;
13. There are a large number of serous effusions that cannot be controlled by treatment (such as pleural effusions, abdominal effusions and pericardial effusions);
14. Have any of the following heart conditions:
15. New York Heart Association (NYHA) Stage III or IV congestive heart failure;
16. Had myocardial infarction or coronary artery bypass grafting (CABG) within ≤6months before enrollment;
17. A history of clinically significant ventricular arrhythmia, or unexplainedsyncope (other than those caused by vasovagal or dehydration);
18. History of severe non-ischemic cardiomyopathy.
19. Known to have active or uncontrolled autoimmune diseases that require treatment withimmunosuppressants, including biologics, such as Crohns disease, rheumatoid arthritis,systemic lupus erythematosus, systemic vasculitis, etc.;
20. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive andperipheral blood hepatitis B virus (HBV) DNA test greater than the normal range;Hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV)RNA detection greater than the normal range; Human immunodeficiency virus (HIV)antibody positive; Syphilis positive; Cytomegalovirus (CMV) DNA test positive;
21. At the time of screening, subjects had venous embolism events (e.g., pulmonaryembolism) and required anticoagulant therapy;
22. Other uncured malignant tumors within the past 3 years or at the same time, exceptcervical carcinoma in situ and skin basal cell carcinoma;
23. Women who are pregnant or nursing, and male or female subjects who plan to have achild within 1 year after receiving C-13-60 cell transfusion;
24. Circumstances deemed unsuitable for participation in the study by other researchers.