scholarly journals Targeting of IL-10R on acute myeloid leukemia blasts with chimeric antigen receptor-expressing T cells

2021 ◽  
Vol 11 (8) ◽  
Author(s):  
Nianci Chen ◽  
Yingxi Xu ◽  
Junli Mou ◽  
Qing Rao ◽  
Haiyan Xing ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Adverse Effects ◽  
Chimeric Antigen Receptor ◽  
Myeloid Leukemia ◽  
Antigen Receptor ◽  
Leukemia Cells ◽  
Car T Cells ◽  
Car T ◽  
Acute Myeloid

AbstractAcute myeloid leukemia (AML) is a biologically and clinically heterogeneous disease with a dismal prognosis and limited treatment options. Chimeric antigen receptor (CAR) T cells have achieved unprecedented clinical responses in patients with B cell malignancies but a dismal consequences in AML. In our previous study, we found that interleukin-10 receptor (IL-10R) was overexpressed in most AML cells, and played an important role in promoting the stemness of leukemia cells. In this study, we developed a novel ligand-based CAR-T cell targeting IL-10R, which displayed striking cytotoxicity both in vitro and in vivo against AML cells. Except for monocytes, it had no significant adverse effects on the normal hematopoietic system, including CD34+ hematopoietic stem and progenitor cells (HSPCs). In addition, even though the incorporation of IL-10 in the CAR cassette led to phenotypes change, it had few adverse effects on the survival and biological activity of IL-10 CAR-T cells and did not cause excessive proliferation of leukemia cells. Therefore, we propose IL-10R is a novel promising therapeutic candidate for AML, and IL-10R targeted CAR-T therapy provides a new treatment strategy to improve the prognosis of AML.

scholarly journals Preclinical Targeting of Human Acute Myeloid Leukemia Using CD4-specific Chimeric Antigen Receptor (CAR) T Cells and NK Cells

2019 ◽  
Vol 10 (18) ◽  
pp. 4408-4419 ◽  
Author(s):  
Huda Salman ◽  
Kevin G. Pinz ◽  
Masayuki Wada ◽  
Xiao Shuai ◽  
Lulu E. Yan ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Nk Cells ◽  
Chimeric Antigen Receptor ◽  
Myeloid Leukemia ◽  
Antigen Receptor ◽  
Car T Cells ◽  
Car T ◽  
Human Acute Myeloid Leukemia ◽  
Acute Myeloid

scholarly journals Chimeric Antigen Receptor-Modified T Cells for the Treatment of Acute Myeloid Leukemia Expressing CD33

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4058-4058 ◽  
Author(s):  
Degang Song ◽  
Michael H. Swartz ◽  
Steve G. Biesecker ◽  
Fernando Borda ◽  
Rutul R. Shah ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Chimeric Antigen Receptor ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Employment Equity ◽  
Car T Cells ◽  
Car T ◽  
Equity Ownership ◽  
Acute Myeloid

Abstract Relapsed acute myeloid leukemia (AML) is an aggressive disease with very poor outcomes. Redirection of T-cell specificity via chimeric antigen receptor (CAR) has shown promising anti-tumor activity in clinical trials, particularly for B cell linage malignancies. CD33 is a transmembrane protein expressed on normal and malignant myeloid-derived cells as well (as on subsets of activated T cells and NK cells). Since this protein is commonly expressed on AML cells, we sought to evaluate the efficacy of targeting AML with CD33-specific CAR-T cells. We generated a lentiviral construct to co-express CD33-specific CAR and a kill switch based on a tag derived from the epidermal growth factor receptor. The latter allows for the conditional elimination of CAR-T cells in vivo. Following transduction of primary T cells, we confirmed CAR and kill switch co-expression by flow cytometry and western blot analyses. Elimination of genetically modified T cells was demonstrated using the clinically-available antibody, cetuximab. CD33 CAR-T cells demonstrated specific cytotoxicity to CD33+ target cell lines. CD33 CAR-T cells were also activated to produce IFNg, TNF, and IL-2 cytokines in response to CD33+ target cells. Furthermore, adoptive transfer of CD33 CAR-T in immunocompromised (NSG) mice bearing established CD33+(CD19neg) AML (MOLM-13) tumor resulted in reduction of tumor burden and improvement of overall survival, compared to control mice receiving CD19 CAR-T cells or no immunotherapy (Figure). Sampling of blood demonstrated the persistence of the CD33 CAR-T cells with no detection of AML (MOLM-13) tumor cells. These pre-clinical data demonstrate the effectiveness of CD33 CAR-T cells in targeting CD33+ AML tumor cells and provide a rationale for future clinical evaluation in AML patients with unmet medical need. Disclosures Song: Intrexon Corporation: Employment, Equity Ownership. Swartz:Intrexon Corporation: Employment, Equity Ownership. Biesecker:Intrexon Corporation: Employment, Equity Ownership. Borda:Intrexon Corporation: Employment. Shah:Intrexon Corporation: Employment, Equity Ownership. Wierda:Genentech: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Novartis: Research Funding; Acerta: Research Funding. Cooper:MD Anderson Cancer Center: Employment; Intrexon: Equity Ownership; Sangamo BioSciences: Patents & Royalties; Targazyme,Inc.,: Equity Ownership; City of Hope: Patents & Royalties; ZIOPHARM Oncology: Employment, Equity Ownership, Patents & Royalties; Miltenyi Biotec: Honoraria; Immatics: Equity Ownership. Chan:Intrexon Corporation: Employment, Equity Ownership.

scholarly journals CAR-T cells targeting CLL-1 as an approach to treat acute myeloid leukemia

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Jinghua Wang ◽  
Siyu Chen ◽  
Wei Xiao ◽  
Wende Li ◽  
Liang Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Car T Cells ◽  
Car T ◽  
Acute Myeloid

scholarly journals In Vitro Pre-Clinical Validation of Suicide Gene Modified Anti-CD33 Redirected Chimeric Antigen Receptor T-Cells for Acute Myeloid Leukemia

PLoS ONE ◽  
2016 ◽  
Vol 11 (12) ◽  
pp. e0166891 ◽  
Author(s):  
Kentaro Minagawa ◽  
Muhammad O. Jamil ◽  
Mustafa AL-Obaidi ◽  
Larisa Pereboeva ◽  
Donna Salzman ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Chimeric Antigen Receptor ◽  
Myeloid Leukemia ◽  
Antigen Receptor ◽  
Suicide Gene ◽  
Clinical Validation ◽  
Acute Myeloid

scholarly journals Targeting FLT3 by chimeric antigen receptor T cells for the treatment of acute myeloid leukemia

Leukemia ◽  
2017 ◽  
Vol 31 (8) ◽  
pp. 1830-1834 ◽  
Author(s):  
L Chen ◽  
H Mao ◽  
J Zhang ◽  
J Chu ◽  
S Devine ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Chimeric Antigen Receptor ◽  
Myeloid Leukemia ◽  
Antigen Receptor ◽  
Acute Myeloid

scholarly journals Chimeric antigen receptor T cell therapies for acute myeloid leukemia

2020 ◽  
Vol 14 (6) ◽  
pp. 701-710
Author(s):  
Bin Gu ◽  
Jianhong Chu ◽  
Depei Wu
Keyword(s):  
Acute Myeloid Leukemia ◽  
T Cell ◽  
Chimeric Antigen Receptor ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Antigen Receptor ◽  
Target Antigen ◽  
Hematopoietic Stem ◽  
Car T ◽  
Acute Myeloid

AbstractChimeric antigen receptor T cell (CAR T) therapies have achieved unprecedented efficacy in B-cell tumors, prompting scientists and doctors to exploit this strategy to treat other tumor types. Acute myeloid leukemia (AML) is a group of heterogeneous myeloid malignancies. Relapse remains the main cause of treatment failure, especially for patients with intermediate or high risk stratification. Allogeneic hematopoietic stem cell transplantation could be an effective therapy because of the graft-versus-leukemia effect, which unfortunately puts the patient at risk of serious complications, such as graft-versus-host disease. Although the identification of an ideal target antigen for AML is challenging, CAR T therapy remains a highly promising strategy for AML patients, particularly for those who are ineligible to receive a transplantation or have positive minimal residual disease. In this review, we focus on the most recent and promising advances in CAR T therapies for AML.

scholarly journals Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor–modified T cells

Blood ◽  
2014 ◽  
Vol 123 (15) ◽  
pp. 2343-2354 ◽  
Author(s):  
Saar Gill ◽  
Sarah K. Tasian ◽  
Marco Ruella ◽  
Olga Shestova ◽  
Yong Li ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Myeloid Leukemia ◽  
Mouse Models ◽  
Chimeric Antigen Receptor ◽  
Myeloid Leukemia ◽  
Antigen Receptor ◽  
Key Points ◽  
Human Acute Myeloid Leukemia ◽  
Engineered T Cells ◽  
Acute Myeloid

Key Points Targeting of CD123 via CAR-engineered T cells results in rejection of human AML and myeloablation in mouse models.

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