This study was a prospective, single-center, open-label, single-arm, multi-dose ascending phase Ⅰ clinical trial. The investigators constructed a TM10-LNP mRNA preparation encoding CTLA-4 antibody and TGF-β trap bifunction protein (YMN-A02 bifunction RNA preparation). The aim of this study is to provide a new strategy for overcoming the immune tolerance of liver tumors and improving the response rate of immunotherapy. The investigators planned to enroll patients with advanced pMMR liver metastasis from colorectal cancer who failed standard treatment. A modified "3+3" design was used, and 10 patients were expected to be enrolled. There were four dose groups of 100μg, 250μg, 500μg and 1000μg. The trial used a modified "3+3" dose climbing design, in which one subject was set as a sentinel patient in the initial 100μg dose group. If the subject did not experience DLT during the DLT observation period, the dose was judged safe and escalation to the next group occurred. If DLT occurred, 3 additional subjects in this group would be required for further evaluation. In the subsequent 250μg, 500μg, and 1000μg dose groups, three subjects were enrolled first in each group: if there was no DLT, the number of subjects was increased. If ≥2 of the 3 cases had DLT, the escalation was terminated. If DLT occurred in 1 out of 3 subjects, 3 additional observations would be made in the same dose group. If the incidence of DLT in the total 6 subjects did not exceed 1/6 after the supplement, the escalation could be escalated. Otherwise, the escalation was terminated and the dose was considered as intolerable.

Inclusion Criteria:

1. Signed the informed consent form approved by the ethics committee.

2. 18-70 years old; ECOG performance status 0-1.

3. Histologically or cytologically confirmed colorectal cancer with liver metastases, molecularly classified as pMMR (presence of other distant metastases allowed).

4. Patients who have failed or are intolerant to standard therapy, or who refuse standard therapy.

   1. For patients with RAS/BRAF wild-type and eligible for targeted therapy: enrollment allowed only after disease progression on a prior standard regimen containing anti-EGFR or anti-VEGF monoclonal antibody.
   2. For patients with BRAF V600E mutation: enrollment allowed only after failure of a prior BRAF inhibitor-containing chemotherapy regimen.
   3. For patients who do not meet the above molecular characteristics: enrollment allowed only after failure of at least two prior lines of systemic chemotherapy (including a platinum-containing regimen).

5. At least one measurable liver metastasis (CT scan long diameter ≥10 mm, slice thickness ≤5 mm).

6. Life Expectancy≥3 months.

7. Adequate Major Organ Function (all within 14 days before randomization):

   1. Hemoglobin ≥80 g/L (no transfusion within 14 days); absolute neutrophil count >1.5×10⁹/L; platelet count ≥80×10⁹/L.
   2. Total bilirubin ≤1.5×ULN; ALT/AST ≤2.5×ULN (or ≤5×ULN in the presence of liver metastases); creatinine clearance ≥60 mL/min (Cockcroft-Gault formula).
   3. Left ventricular ejection fraction (LVEF) ≥50%.

8. Good compliance, and family agrees to cooperate with survival follow-up.

Exclusion Criteria:

1. Participation in another interventional drug trial within 4 weeks before enrollment.
2. Prior or concurrent other malignancy, except: carcinoma in situ of the cervix, cutaneous squamous cell carcinoma, superficial bladder tumor, or any other malignancy that has been curatively treated and recurrence-free for ≥5 years.
3. Poorly controlled heart disease or clinical symptoms, including but not limited to: NYHA class ≥2 heart failure, unstable angina, myocardial infarction within 1 year, or clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
4. Pregnant or breastfeeding women.
5. Active infection, including but not limited to: active tuberculosis, systemic bacterial or fungal infection (NCI-CTCAE v5.0 grade ≥2), HIV infection, active HBV (HBV DNA >ULN), or active HCV (HCV RNA >ULN).
6. History of substance abuse that cannot be abstained from, or history of psychiatric disorders.
7. Active or history of autoimmune disease (including but not limited to uveitis, enteritis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism, etc.). Exceptions: vitiligo controlled with only topical agents; childhood asthma completely resolved without any intervention in adulthood. Patients with asthma requiring bronchodilators for medical intervention are excluded.
8. Prior vaccination with any mRNA-based drug or mRNA formulation.
9. Prior participation in any clinical trial involving lipid nanoparticle (LNP) formulations.
10. Contraindications to intravenous infusion.
11. History of drug abuse, or any medical, psychological, or social condition (e.g., alcoholism or drug addiction) that, in the investigator's judgment, may affect study compliance.
12. Known allergy, hypersensitivity, or intolerance to any component (active substance or excipients) of the study drug; history of severe allergy to drugs, food, or vaccines, including but not limited to anaphylactic shock, angioedema of the larynx, anaphylactic dyspnea, allergic purpura, thrombocytopenic purpura, or Arthus reaction.
13. Plan to conceive (either female subject or partner of male subject) from screening through 12 months after the last dose.
14. Any concurrent condition that, in the investigator's judgment, may compromise patient safety or interfere with study completion.