CD133-directed CAR T cells for advanced metastasis malignancies: A phase I trial
| Autor: | Haiyan Lv, Kaichao Feng, Weidong Han, Can Luo, Chuan Tong, Yao Wang, Yang Liu, Qingming Yang, Xiaolei Li, Zhiqiang Wu, Hanren Dai, Yelei Guo, Meixia Chen, Jianhua Huang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine autologous T cells Immunology lcsh:RC254-282 Metastasis phase I trial advanced metastasis malignancies 03 medical and health sciences fluids and secretions 0302 clinical medicine Text mining Antigen Cancer stem cell therapeutic trials Immunology and Allergy Medicine CD133 neoplasms chimeric antigen receptor (CAR) Original Research business.industry lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Adoptive T cell therapies Therapeutic trial Epithelium carbohydrates (lipids) Autologous T-cells 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis embryonic structures cardiovascular system Cancer research Car t cells lcsh:RC581-607 business |
| Zdroj: | Oncoimmunology OncoImmunology, Vol 7, Iss 7 (2018) |
| ISSN: | 2162-402X |
| Popis: | Expressed by cancer stem cells of various epithelial cell origins, CD133 is an attractive therapeutic target for cancers. Autologous chimeric antigen receptor-modified T-cell directed CD133 (CART-133) was first tested in this trial. The anti-tumor specificity and the postulated toxicities of CART-133 were first assessed. Then, we conducted a phase I clinical study in which patients with advanced and CD133-positive tumors received CART-133 cell-infusion. We enrolled 23 patients (14 with hepatocellular carcinoma [HCC], 7 with pancreatic carcinomas, and 2 with colorectal carcinomas). The 8 initially enrolled patients with HCC were treated by a CART-133 cell dose escalation scheme (0.05–2 × 106/kg). The higher CAR-copy numbers and its reverse relationship with the count of CD133+ cells in peripheral blood led to the determination of an acceptable cell dose is 0.5–2 × 106/kg and reinfusion cycle in 23 patients. The primary toxicity is a decrease in hemoglobin/platelet (≤ grade 3) that is self-recovered within 1 week. Of 23 patients, three achieved partial remission, and 14 achieved stable disease. The 3-month disease control rate was 65.2%, and the median progression-free survival was 5 months. Repeated cell infusions seemed to provide a longer period of disease stability, especially in patients who achieved tumor reduction after the first cell-infusion. 21 out of 23 patients had not developed detectable de novo lesions during this term. Analysis of biopsied tissues by immunohistochemistry showed CD133+ cells were eliminated after CART-133 infusions. This trial showed the feasibility, controllable toxicities, and effective activity of CART-133 transfer for treating patients with CD133-postive and late-stage metastasis malignancies. |
| Databáze: | OpenAIRE |
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