CD133-directed CAR T cells for advanced metastasis malignancies: A phase I trial

Area of Science:

• Oncology
• Immunotherapy
• Cell Therapy

Background:

• CD133 is a cell surface marker expressed on cancer stem cells of various epithelial cancers.
• CD133 presents an attractive target for novel cancer therapies.
• Chimeric antigen receptor (CAR) T-cell therapy has emerged as a powerful tool in cancer treatment.

Purpose of the Study:

• To assess the anti-tumor specificity and toxicities of autologous CART-133 therapy.
• To evaluate the safety and efficacy of CART-133 cell infusion in patients with advanced, CD133-positive malignancies.
• To determine an optimal dosing and reinfusion schedule for CART-133 therapy.

Main Methods:

• A phase I clinical study was conducted involving 23 patients with advanced CD133-positive tumors (14 HCC, 7 pancreatic, 2 colorectal).
• Initial dose escalation was performed in 8 HCC patients (0.05-2 × 10^6/kg).
• Subsequent analysis informed an acceptable cell dose of 0.5-2 × 10^6/kg and reinfusion cycle for all 23 patients.

Main Results:

• The primary toxicity observed was a transient decrease in hemoglobin/platelets (≤ grade 3), self-recovering within one week.
• Three patients achieved partial remission, and 14 had stable disease, resulting in a 3-month disease control rate of 65.2%.
• Median progression-free survival was 5 months, with repeated infusions potentially prolonging disease stability and elimination of CD133+ cells observed in biopsied tissues.

Conclusions:

• Autologous CART-133 cell transfer is feasible and demonstrates controllable toxicities in patients with CD133-positive advanced metastatic malignancies.
• CART-133 therapy shows effective anti-tumor activity, supporting its further investigation in clinical settings.
• The study established an acceptable dose and reinfusion schedule for CART-133, paving the way for future therapeutic applications.