Using modified stem cells to treat advanced colorectal cancer

CXCL Chemokine and TNF Superfamily Co-stimulatory Molecule-modified Mesenchymal Stem Cells for the Treatment of Advanced Colorectal Cancer

This study is testing if specially modified stem cells from umbilical cords can help boost the immune system in people with advanced colorectal cancer who haven't responded to regular treatments.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai East Hospital (Academic / other)
• Drugs / interventions: prednisone
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06446050 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of human umbilical cord-derived mesenchymal stem cells (MSCs) that have been engineered to express antitumor chemokines and co-stimulatory molecules. The modified MSCs are administered intravenously every 21 days to patients with advanced colorectal cancer, aiming to enhance the immune response against tumors. By migrating to solid tumors, these cells attract and stimulate lymphocytes, potentially improving antitumor immunity in patients who have not responded well to standard treatments. The trial will determine the optimal dosing regimen for these MSCs.

Who should consider this trial

Good fit: Ideal candidates include patients under 18 years old with metastatic or locally advanced colorectal cancer who have progressed on or are intolerant to standard treatments.

Not a fit: Patients with colorectal cancer who are not eligible due to age or those who have not progressed on standard treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new immunotherapeutic option for patients with advanced colorectal cancer who have limited treatment options.

How similar studies have performed: While the approach of using modified MSCs for cancer treatment is innovative, similar studies have shown promise in enhancing immune responses, though this specific application is relatively novel.

Eligibility criteria

Inclusion Criteria (Participants must meet all of the following selection criteria in order to participate in this study):

1. Age less than 18 years old (including 18 years old), regardless of gender;
2. Patients with metastatic or locally advanced colorectal cancer confirmed by pathological histology or cytology;
3. According to the Efficacy Evaluation Criteria for Solid Tumors (RECIST) version 1.1, there are very few measurable tumor lesions;
4. Individuals who have progressed or are intolerant to standard treatment in the past, or patients who refuse standard treatment;
5. Severe abnormalities in the fluid system, liver and kidney function: lymphocyte count ≥ 0.8 × 10\^9/L, absolute neutrophil count ≥ 1.5 × 10\^9/L, hemoglobin ≥ 9g/dL, platelet count ≥ 75 × 10\^9/L; Alanine aminotransferase (ALT) ≤ 3 times upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 3 times ULN, creatinine ≤ 1.5 times ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 times ULN, prothrombin time (PT) ≤ 1.5 times ULN, international standardized mean value (INR) ≤ 1.5 times ULN;
6. Eastern Cooperative Oncology Group (ECOG) score 0-2;
7. Patients with fertility must agree to use reliable contraceptive methods (hormone or barrier method or abstinence) during the trial period and at least 12 weeks after the last treatment;
8. Patients who have not undergone any other adoptive immune cell therapy or stem cell therapy within two years;
9. The patient is willing to participate and sign an informed consent form in writing.

Exclusion Criteria (Subjects with any of the following characteristics are not eligible to participate in this study):

1. Individuals with a history of allergies to biological agents or allergies to any ingredients used for cell culture;
2. Pregnant or lactating individuals;
3. Expected shelf life of more than 3 months;
4. Active infections that require systemic treatment or uncontrollable infections;
5. The adverse reactions of previous anti-tumor treatments have not yet recovered to Common Terminology Criteria for Adverse Events 4.03 (CTCAE4.03) level evaluation ≤ 1 level (excluding hair loss);
6. Have a history of severe cerebrovascular diseases, including but not limited to ventricular arrhythmias that require clinical intervention; Within 6 months, there have been acute coronary syndrome, myocardial infarction, congestive heart failure, stroke, or other Grade III or higher cardiovascular events; The New York Heart Association (NYHA) Heart Function Rating ≥ Grade II or Left Ventricular Ejection Score (LVEF) \<50%; Poor control of hypertension despite standard treatment (systolic blood pressure \>150mmHg, diastolic blood pressure \>90mmHg);
7. A history of severe pulmonary parenchyma or pulmonary vascular related diseases, including but not limited to high-risk individuals for venous thromboembolism (VTE) (Padua score ≥ 4), as outlined in the Chinese Consensus of Cardiopulmonary Resuscitation Experts on Venous Thromboembolism Cardiac Arrest (CA) Guidelines; Or oxygen may be needed to maintain sufficient blood oxygen saturation (≥ 95%);
8. Patients with clinical symptoms of central nervous system metastasis and/or cancerous meningitis (patients with stable brain metastasis can be grouped), and those suspected of central nervous system or leptomeningeal metastasis need CT/MRI examination to rule them out;
9. Individuals with clinically confirmed autoimmune diseases (excluding thyroiditis);
10. Individuals with HIV infection; Individuals with acute Epstein-Barr virus (EBV) or cytomegalovirus (CMV) virus infection;
11. Patients with active replication of hepatitis B virus (DNA \> 1000 cps/mL), hepatitis C patients;
12. Individuals who have received allogeneic bone marrow transplantation in the past;
13. Immunosuppressive subjects, including known immunodeficiencies; Within 14 days before the first dose of cell therapy and during the study period, those who require systemic use of steroid drugs (prednisone \>10mg/day or equivalent doses of similar drugs) or other immunosuppressants (excluding those who have recently or recently used systemic steroids, or short-term use of steroid drugs for preventive treatment);
14. Known to have alcohol or drug dependence;
15. The researcher assessed that there may be medical history or disease, treatment or abnormal experimental values that may hinder the full participation of the subjects in this clinical study, or other situations that are not suitable for participation in this clinical study.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai East Hospital (South Division) — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Yong Gao, MD — Shanghai East Hospital
• Study coordinator: Yanan Hai, MD

Conditions Advanced Colorectal Cancer