The aim of this study is to assess the safety and efficacy of human umbilical cord-derived allogenic mesenchymal stem cells (MSCs) engineered to express antitumor chemokine and co-stimulatory molecule. Following systemic administration, these cells are able to migrate into solid tumors such as colorectal tumors. Once enriched in the tumor, they will attract peripheral lymphocytes consisting of T and natural killer (NK) cells, and simultaneously stimulate the infiltrated lymphocytes for persistent and enhanced antitumor immunity. Thus, this MSC-based treatment provides a potentially effective and targeted immunotherapeutic strategy for tumors with unfavorable immune microenvironment and possibly poor response to immune checkpoint blockade (ICB).
During this investigator-initiated trial (IIT), colorectal cancer patients will receive modified MSCs every 21 days via intravenous infusion. Increasing does will be tested in the initial cohort and an optimal dose will be chosen for the remaining patients.
Age less than 18 years old (including 18 years old), regardless of gender;
Patients with metastatic or locally advanced colorectal cancer confirmed by pathological histology or cytology;
According to the Efficacy Evaluation Criteria for Solid Tumors (RECIST) version 1.1, there are very few measurable tumor lesions;
Individuals who have progressed or are intolerant to standard treatment in the past, or patients who refuse standard treatment;
Individuals with a history of allergies to biological agents or allergies to any ingredients used for cell culture;
Pregnant or lactating individuals;
Expected shelf life of more than 3 months;
Active infections that require systemic treatment or uncontrollable infections;
Single group
MSC-L
Biological/VaccineHuman umbilical cord-derived mesenchymal stem cells (MSCs) genetically modified to express antitumor chemokine and co-stimulatory molecule will be administered intravenously at a dose of 1/2/3 x 10\^6 cells/kg, every 21 days for at least 6 cycles of treatment.
Dose-Limiting Toxicities rate (DLT)
Proportion of patients who has experienced a DLT
Adverse Event (AE)
Proportion of patients who has experienced an AE
Determination of optimal dose of MSC-L
The largest dose that has an estimated risk of causing DLT (defined as MSC-L related adverse event of grade 3 or higher) equal or closest to the target level of 35% (the target toxicity level).
Disease Control Rate (DCR)
Percentage of patients cancer whose MSC-L treatment has led to a complete response, partial response, or stable disease.
Progression-free survival (PFS)
Time from the date of first dose of study treatment to the date of progression or death from any cause.
Overall Survival (OS)
Time from the date of first dose of study treatment to the date of death.
MSC-L kinetics in peripheral blood
Quantification of circulating MSC-L in the blood.
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