In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 3042-3042
Abstract:
3042 Background: Expressed by cancer stem cells of various epithelial cell origins, CD133 is an attractive therapeutic target for cancers. Autologous chimeric antigen receptor-modified T cells directed CD133 (CART-133) were firstly tested in this clinical trial. We aimed to determine the safety dosage, toxicity and biological activity of CART-133 in epithelium-derived solid tumors. Methods: The initially enrolled 8 patients with sorafenib-refractory hepatocellular carcinoma (HCC), treated by CART-133 monotherapy, were assigned into 3 dose cohorts (1, 0.5-1.5×10 5 /kg; 2, 5-10×10 5 /kg; 3, 1-2×10 6 /kg). For the additional 16 patients (6 HCCs, 7 pancreatic carcinomas, 2 colorectal carcinomas, and 1 cholangiocarcinoma), all non-HCCs were conditioned by regimen (Nab-pacitaxel/cyclophosphamide or anti-PD1 antibody) before cell infusions. Results: For the initial 8 HCCs, 1 from cohort 2 occurred hemoglobin/platelet decline and direct hyperbilirubinemia (Grade 3), 4 from cohort 2/3 reported delayed low fever, nausea accompanied with elevation of CRP and serum cytokines. The 4-6 week persistence of relatively higher CAR copy numbers and its reverse relationship with the count of CD133 + cells harboring pro-metastatic epithelial progenitor cells in peripheral blood led to the determination of acceptable cell infusion dose from 0.5 to 2×10 6 /kg and reinfusion cycle in 24 patients. Similar toxicities ( ≤ Grade 3) were observed in 15 cases. The cholangiocarcinoma patient who uniquely received 1 cycle of CART-133 infusion after anti-PD1, developed Grade 3 skin/mucosal vasculature damage, blood three-lineage decline and cytokine release syndrome, whereas, obtained a 4.5 month-lasting partial remission. Although no marked reduction of tumor volume was observed in most patients, 21 out of 23 patients had an 8-22 week progression-free survival, 2 patients without bulky tumor burden attained 8/10-month ongoing stable disease by the cut-off data (Jan 1, 2017). Conclusions: This trial showed the feasibility, controllable toxicities and effective biological activity of CART-133 transfer for the treatment of late-stage tumor patients. Clinical trial information: NCT02541370.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2017.35.15_suppl.3042
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2017
detail.hit.zdb_id:
2005181-5
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