Bibliographic Details
| Title: |
Head-to-head comparison of in-house produced CD19 CAR-T cell in ALL and NHL patients |
| Authors: |
Elad Jacoby, Orit Itzhaki, Abraham Nissani, Michal Levi, Arnon Nagler, Adva Kubi, Karin Brezinger, Hadar Brayer, Li-at Zeltzer, Meir Rozenbaum, Helly Vernitsky, Amos Toren, Abraham Avigdor |
| Source: |
Journal for ImmunoTherapy of Cancer, Vol 8, Iss 1 (2020) |
| Publisher Information: |
BMJ Publishing Group, 2020. |
| Publication Year: |
2020 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
Background CD19 chimeric antigen receptor T (CAR-T) cells demonstrate remarkable remission rates in pediatric and adult patients with refractory or relapsed (r/r) acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). In 2016, we initiated a clinical trial with in-house produced CD19 CAR-T cells with a CD28 co-stimulatory domain. We analyzed, for the first time, differences in production features and phenotype between ALL and NHL patients.Methods Non-cryopreserved CAR-T cells were produced from patients’ peripheral blood mononuclear cells within 9 to 10 days. 93 patients with r/r ALL and NHL were enrolled under the same study. CAR-T cells of ALL and NHL patients were produced simultaneously, allowing the head-to-head comparison.Results All patients were heavily pretreated. Three patients dropped out from the study due to clinical deterioration (n=2) or production failure (n=1). Cells of ALL patients (n=37) expanded significantly better and contained more CAR-T cells than of NHL patients (n=53). Young age had a positive impact on the proliferation capacity. The infusion products from ALL patients contained significantly more naïve CAR-T cells and a significantly higher expression of the chemokine receptor CXCR3. PD-1, LAG-3, TIM-3, and CD28 were equally expressed. 100% of ALL patients and 94% of NHL patients received the target dose of 1×10e6 CAR-T/kg. The overall response rate was 84% (30/36) in ALL and 62% (32/52) in NHL. We further compared CAR-T cell infusion products to tumor infiltrating lymphocytes (TIL), another common type of T cell therapy, mainly clinically effective in solid tumors. CAR-T cells contained significantly more naïve T cells and central memory T cells and significantly less CCR5 compared to TIL infusion products.Conclusions The in-house production of CAR-T cells is highly efficient and fast. Clinical response rate is high. CAR-T cells can be successfully produced for 99% of patients in just 9 to 10 days. Cells derived from ALL patients demonstrate a higher proliferation rate and contain higher frequencies of CAR-T cells and naïve T cells than of NHL patients. In addition, understanding the differences between CAR-T and TIL infusion products, may provide an angle to develop CAR-T cells for the treatment of solid tumors in the future.Trial registration number ClinicalTrials.gov; CAR-T: NCT02772198, First posted: May 13, 2016; TIL: NCT00287131, First posted: February 6, 2006. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2051-1426 |
| Relation: |
https://jitc.bmj.com/content/8/1/e000148.full; https://doaj.org/toc/2051-1426 |
| DOI: |
10.1136/jitc-2019-000148 |
| Access URL: |
https://doaj.org/article/c3d688963adb46cfae5f74024ca43fb3 |
| Accession Number: |
edsdoj.3d688963adb46cfae5f74024ca43fb3 |
| Database: |
Directory of Open Access Journals |
