KRAS-Specific Autologous TCR-T Cell Therapy for KRAS Mutation in Advanced Solid Tumors

Prior treatment

• 1.Prior treatment with gene-modified T-cell therapies.
• Current treatment with T-cell suppressive agents (e.g., cyclophosphamide, FK506, tripterygium glycosides) or T-cell stimulants.
• Chemotherapy, targeted therapy, immunotherapy, or investigational drugs administered within 2 weeks, or radiotherapy within 4 weeks prior to enrollment.
• Symptomatic brain metastases unless stabilized with prior treatment (e.g., surgery or radiotherapy).

Other illness

• Presence of serious diseases and comorbidities, including but not limited to: severe heart disease, cerebrovascular disease, seizures, poorly controlled diabetes (such as Type 1 diabetes or insulin-dependent diabetes), pancreatic dysfunction, severe infections, active gastrointestinal ulcers, gastrointestinal bleeding, mechanical or paralytic bowel obstruction, pulmonary fibrosis, renal failure, respiratory failure, etc.
• History of severe cardiovascular diseases within the past 6 months, including but not limited to: myocardial infarction, severe or unstable angina, coronary artery or peripheral artery bypass surgery, New York Heart Association (NYHA) Class III or IV heart failure, etc.
• Known history of myelodysplastic syndrome, lymphoma, or other malignancies.
• Active autoimmune diseases, including but not limited to acquired/congenital immunodeficiency, organ transplantation, autoimmune hepatitis, systemic lupus erythematosus, or inflammatory bowel disease.
• Active hepatitis B, hepatitis C, or HIV infection.
• Uncontrolled mental or neurological disorders.
• Any condition deemed unsuitable for study participation by the investigator.

Lab values

• Significant organ dysfunction, as evidenced by:
  • leukocytes\<3.0 x 109/L
  • absolute neutrophil count \>1.5 x 109/L
  • hemoglobin\<90g/L
  • platelets \<100 x 109/L
  • Creatinine\>1.5×ULN or creatinine clearance \<50mL/min
  • lymphocytes\<0.5 x 109/L
  • total bilirubin\>3×ULN; ALT/AST\>3×ULN (or \>5× ULN in patients with liver metastases)
  • INR/APTT\>1.5×ULN；
  • SpO2≤93%
• Left ventricular ejection fraction (LVEF) \< 50%.
• Known allergy to albumin, investigational drugs, or their excipients.

Other

• Pregnancy or breastfeeding.

• Patients aged 18-70 years.
• Histologically or cytologically confirmed advanced solid tumors (e.g., colorectal cancer, pancreatic cancer, NSCLC) with KRAS G12V mutations and HLA-A\*11:01 genotype.
• Failed standard therapies or no effective treatment available.
• ECOG performance status of 0-1.
• Life expectancy of ≥3 months.
• Presence of at least one measurable lesion as defined by RECIST 1.1 criteria.
• Female patients of childbearing potential must agree to use highly effective contraceptive methods during the study and for at least 6 months after the last dose. A negative pregnancy test within 7 days prior to treatment initiation is required.
• Written informed consent provided by the patient, with an expectation of compliance with study procedures.