A Cell-Based Artificial Antigen-Presenting Cell Coated with Anti-CD3 and CD28 Antibodies Enables Rapid Expansion and Long-Term Growth of CD4 T Lymphocytes

2002 ◽  
Vol 105 (3) ◽  
pp. 259-272 ◽  
Author(s):  
Anna K. Thomas ◽  
Marcela V. Maus ◽  
Waleed S. Shalaby ◽  
Carl H. June ◽  
James L. Riley
Keyword(s):  
T Lymphocytes ◽  
Rapid Expansion ◽  
Antigen Presenting Cell ◽  
Artificial Antigen ◽  
A Cell ◽  
Antigen Presenting

scholarly journals Establishment and Characterization of a Cell Based Artificial Antigen-Presenting Cell for Expansion and Activation of CD8+ T Cells Ex Vivo

2008 ◽  
Vol 5 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Weijuan Gong ◽  
Mingchun Ji ◽  
Zhengfeng Cao ◽  
Liheng Wang ◽  
Yayun Qian ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Ex Vivo ◽  
Antigen Presenting Cell ◽  
Artificial Antigen ◽  
A Cell ◽  
Antigen Presenting

scholarly journals Rapid Expansion of Highly Functional Antigen-Specific T Cells from Patients with Melanoma by Nanoscale Artificial Antigen-Presenting Cells

2020 ◽  
Vol 26 (13) ◽  
pp. 3384-3396 ◽  
Author(s):  
Junya Ichikawa ◽  
Tatsuya Yoshida ◽  
Ariel Isser ◽  
Andressa S. Laino ◽  
Melinda Vassallo ◽  
...  
Keyword(s):  
T Cells ◽  
Antigen Presenting Cells ◽  
Rapid Expansion ◽  
Artificial Antigen ◽  
Antigen Presenting

Artificial Antigen Presenting Cell Can Be Used To Propagate Genetically Modified CD19-Specific T Cells through Chimeric Antigen Receptor.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1295-1295
Author(s):  
Tontanai Numbenjapon ◽  
Lisa Marie A. Serrano ◽  
Simon Olivares ◽  
Wen-Chung Chang ◽  
Harjeet Singh ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Chimeric Antigen Receptor ◽  
Cell Activation ◽  
Genetically Modified ◽  
K562 Cells ◽  
Antigen Presenting Cell ◽  
Artificial Antigen ◽  
Antigen Presenting

Abstract The safety and feasibility of adoptive immunotherapy, using CD19-specific T cells that have been genetically modified to express a chimeric antigen receptor (CAR) and numerically expanded ex vivo, need to be addressed. Second-generation trials are being developed incorporating improvements into the design of the CAR as well as the manufacturing processes. Here we describe a platform for propagating CD19-specific T cells through an artificial antigen presenting cell (aAPC) which co-expresses CD19 and T-cell co-stimulatory molecules to provide a fully-competent T-cell activation signal leading to T-cell proliferation. K562 cells were selected as the platform for the aAPCs since (i) they have previously been used in compliance with current good manufacturing practice (cGMP), (ii) they express the desired endogenous T-cell adhesion molecules, and (iii) they fail to express classical HLA class I/II molecules and thus are not targets for a T-cell mediated allogeneic immune response. Therefore, K562 cells were genetically modified to co-express CD19 and both of the T-cell co-stimulatory molecules 4-1BBL (CD137L) and MICA. We then tested the ability of these K562 aAPCs to expand T cells expressing a new CD19-specific CAR designated CD19RCD28. This CAR utilizes a CD19-specific scFv to bind to CD19 independent of MHC and confers an activation signal to genetically modified T cells through both CD28 and CD3-ζ. The CD19RCD28+ T cells could be rapidly expanded (50-fold in 14 days) when cultured in the presence of recombinant human IL-2 and irradiated K562 aAPCs (1:50 ratio, T cell to aAPC). The use of freshly thawed aAPCs improved the practicality of using this antigen-driven expansion method in compliance with cGMP. The numerical expansion of the genetically modified T cells was associated with an increased CAR cell-surface expression, from 17 ± 11% (mean ± SD) before co-culture compared with 44 ± 8% (mean ± SD) after co-culture with the aAPCs, which is consistent with T-cell activation through the CAR. A 3H-thymidine incorporation assay was used to demonstrate that CD19 on the K562 aAPC was necessary, but not sufficient, to proliferate CD19RCD28+ T cells. Furthermore, this proliferation assay demonstrated that co-expression of both 4-1BBL (CD137L) and MICA along with CD19 resulted in the most efficient proliferation of the genetically modified T cells. The propagation of CAR+ T cells on antigen+ aAPCs may thus (i) avoid the need for allogeneic peripheral blood mononuclear feeder cells, which are expensive and time-consuming to prepare in compliance with cGMP, (ii) select in vitro for genetically modified T cells with proven CAR-dependent replicative capacity, and (iii) provide conditions for the outgrowth of subpopulations of T cells within a bulk culture that have increased transgene expression. The feasibility of this new T-cell propagation method using aAPC will be tested in the upcoming clinical trials.

scholarly journals Long-Lived Antitumor CD8+ Lymphocytes for Adoptive Therapy Generated Using an Artificial Antigen-Presenting Cell

2007 ◽  
Vol 13 (6) ◽  
pp. 1857-1867 ◽  
Author(s):  
Marcus O. Butler ◽  
Jeng-Shin Lee ◽  
Sascha Ansén ◽  
Donna Neuberg ◽  
F. Stephen Hodi ◽  
...  
Keyword(s):  
Antigen Presenting Cell ◽  
Adoptive Therapy ◽  
Artificial Antigen ◽  
Antigen Presenting

scholarly journals Rapid Expansion of Tumor-Specific T Cells Using Nanoparticle-Based Artificial Antigen Presenting Cells (aAPCs)

2016 ◽  
Vol 22 (3) ◽  
pp. S146-S147
Author(s):  
Juan Carlos Varela ◽  
Christian Schuetz ◽  
Mathias Oelke ◽  
Jonathan Schneck
Keyword(s):  
T Cells ◽  
Antigen Presenting Cells ◽  
Rapid Expansion ◽  
Artificial Antigen ◽  
Antigen Presenting

scholarly journals An Artificial Antigen-presenting Cell with Paracrine Delivery of IL-2 Impacts the Magnitude and Direction of the T Cell Response

2011 ◽  
Vol 286 (40) ◽  
pp. 34883-34892 ◽  
Author(s):  
Erin R. Steenblock ◽  
Tarek Fadel ◽  
Michael Labowsky ◽  
Jordan S. Pober ◽  
Tarek M. Fahmy
Keyword(s):  
T Cell ◽  
Cell Response ◽  
T Cell Response ◽  
Antigen Presenting Cell ◽  
Artificial Antigen ◽  
Antigen Presenting
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