Immunotherapy of acute leukemia by chimeric antigen receptor-modified lymphocytes using an improved Sleeping Beauty transposon platform Article Swipe
Chiara F. Magnani
,
Nice Turazzi
,
Fabrizio Benedicenti
,
Andrea Calabria
,
Erika Tenderini
,
Sarah Tettamanti
,
Greta Maria Paola Giordano Attianese
,
Laurence J.N. Cooper
,
Alessandro Aiuti
,
Eugenio Montini
,
Andrea Biondi
,
Ettore Biagi
·
YOU?
·
· 2016
· Open Access
·
· DOI: https://doi.org/10.18632/oncotarget.9955
YOU?
·
· 2016
· Open Access
·
· DOI: https://doi.org/10.18632/oncotarget.9955
Chimeric antigen receptor (CAR)-modified T-cell adoptive immunotherapy is a remarkable therapeutic option proven effective in the treatment of hematological malignancies. In order to optimize cell manufacturing, we sought to develop a novel clinical-grade protocol to obtain CAR-modified cytokine-induced killer cells (CIKs) using the Sleeping Beauty (SB) transposon system. Administration of irradiated PBMCs overcame cell death of stimulating cells induced by non-viral transfection, enabling robust gene transfer together with efficient T-cell expansion. Upon single stimulation, we reached an average of 60% expression of CD123- and CD19- specific 3rd generation CARs (CD28/OX40/TCRzeta). Furthermore, modified cells displayed persistence of cell subsets with memory phenotype, specific and effective lytic activity against leukemic cell lines and primary blasts, cytokine secretion, and proliferation. Adoptive transfer of CD123.CAR or CD19.CAR lymphocytes led to a significant anti-tumor response against acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) disseminated diseases in NSG mice. Notably, we found no evidence of integration enrichment near cancer genes and transposase expression at the end of the differentiation. Taken all together, our findings describe a novel donor-derived non-viral CAR approach that may widen the repertoire of available methods for T cell-based immunotherapy.
Related Topics
Concepts
Chimeric antigen receptor
Immunotherapy
Cancer research
Immunology
Adoptive cell transfer
Leukemia
CD19
CD28
Medicine
Cancer immunotherapy
Antigen
Biology
T cell
Immune system
CD8
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.18632/oncotarget.9955
- http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=9955&path%5B%5D=31290
- OA Status
- diamond
- Cited By
- 48
- References
- 54
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2436952019
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W2436952019Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.18632/oncotarget.9955Digital Object Identifier
- Title
-
Immunotherapy of acute leukemia by chimeric antigen receptor-modified lymphocytes using an improved Sleeping Beauty transposon platformWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2016Year of publication
- Publication date
-
2016-06-13Full publication date if available
- Authors
-
Chiara F. Magnani, Nice Turazzi, Fabrizio Benedicenti, Andrea Calabria, Erika Tenderini, Sarah Tettamanti, Greta Maria Paola Giordano Attianese, Laurence J.N. Cooper, Alessandro Aiuti, Eugenio Montini, Andrea Biondi, Ettore BiagiList of authors in order
- Landing page
-
https://doi.org/10.18632/oncotarget.9955Publisher landing page
- PDF URL
-
https://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=9955&path%5B%5D=31290Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
diamondOpen access status per OpenAlex
- OA URL
-
https://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=9955&path%5B%5D=31290Direct OA link when available
- Concepts
-
Chimeric antigen receptor, Immunotherapy, Cancer research, Immunology, Adoptive cell transfer, Leukemia, CD19, CD28, Medicine, Cancer immunotherapy, Antigen, Biology, T cell, Immune system, CD8Top concepts (fields/topics) attached by OpenAlex
- Cited by
-
48Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 1, 2024: 4, 2023: 7, 2022: 3, 2021: 6Per-year citation counts (last 5 years)
- References (count)
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54Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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