This project plans to use CIK combined with chemotherapy, immunotherapy and targeted therapy to treat CRC patients, so as to explore the effectiveness of CIK treatment and the CRC subtypes more suitable for CIK treatment, thereby improving the survival rate and quality of life of CRC patients.

Colorectal cancer (CRC) is a malignant tumor that seriously threatens human health, and according to the international agency for research on cancer (IARC) data, in 2018, the number of new cases of CRC totalled more than 1.8 million and the number of deaths totalled more than 88million, making it the third most common cancer worldwide [1]. In recent years, with the development of economic level in China, changes in lifestyle and dietary structure, the incidence and mortality of CRC have shown a continuous increasing trend, and it is ranked 5th in all malignant tumors. According to statistics, at present, our country has 376000 new CRC cases and 191000 deaths annually, and the whole face extremely serious challenges.

Patients with advanced CRC have a more complicated disease, and the 5-year survival rate is even less than 5%. A single therapeutic means cannot achieve the desired therapeutic effect, and often multiple therapeutic modalities are used for intervention, including surgery, radiotherapy, chemotherapy, interventional minimally invasive treatment, immunotherapy and molecular targeting, etc. Because of the potential efficacy of CIK treatment in controlling tumor growth and prolonging patient survival, but there are still few clinical studies about CIK combined with other treatment modalities, this protocol is intended to use CIK combined with chemotherapy, immune and targeted therapy in CRC patients, in order to explore the effectiveness of CIK treatment and more suitable CRC subtypes for CIK treatment, and then improve the survival rate and quality of life of CRC patients.

Inclusion Criteria:

• Age range 18-70 years;

  • Patients diagnosed with colorectal cancer, TNM stage III-IV;

    • Had at least one extracranially measurable lesion by recist1.1 criteria; ④ Patients who had failed at least one or two prior lines of standard therapy or relapsed, or who were intolerant to or voluntarily abandoned one or two prior lines of standard therapy; ⑤ Expected survival ≥ 90 days;

      • The major organs function normally; ⑦ The subject voluntarily joined this study, signed the informed consent, complied well and cooperated with the follow-up.

Exclusion Criteria:

• Had participated in other clinical trialists of drugs within 4 weeks before the start of the study;

  • Those who had hypertension that was inadequately controlled with a single antihypertensive agent (systolic blood pressure > 140 mmHg and diastolic blood pressure > 90 mmHg, as judged by the investigator), had myocardial ischemia or myocardial infarction of grade I or higher, arrhythmia of grade I and higher (including QT interval ≥ 440 MS), or cardiac dysfunction;

    • Those with a history of substance abuse who are unable to abstain or who have a history of mental disorders;

      • Presence of fungal, bacterial, viral, or other infections that are not controllable or require antibiotic therapy;

        • For subjects with prior chemotherapy use, ≥ grade 2 hematologic toxicity, or ≥ grade 3 nonhematologic toxicity according to nci-ctcae 5.0 criteria at enrollment; ⑥ Known presence of a history of HIV, or hepatitis B (HBsAg positive) or hepatitis C virus (anti HCV positive) nucleic acid test positive;

          • Presence of any indwelling catheter or drain (eg, biliary drain or pleural / peritoneal / pericardial catheter). Use of a dedicated central venous catheter was permitted (colostomy for patients with bowel cancer, percutaneous nephrostomy tube, indwelling Frey catheter, considered by the investigator for implications); ⑧ Presence of brain metastases, presence of a history or disease of the CNS such as seizure disorders, cerebral ischemia / hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the CNS;