REGENERATION OF WT1 SPECIFIC CTLS UTILIZING IPSC TECHNOLOGY
(Abstract release date: 05/19/16)
EHA Library. Maeda T. 06/11/16; 135269; S513
Dr. Takuya Maeda
Contributions
Contributions
Abstract
Abstract: S513
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Hall C14
Background
Current cancer immunotherapies mainly aim to activate and expand tumor antigen specific cytotoxic T lymphocytes (CTLs) in vitro or in vivo, but these methods are not so successuful because of the difficulty in preparing sufficient number of CTLs.
Aims
For successful cancer immunotherapy, we are trying to expand tumor antigen specific cytotoxic T lymphocytes (CTLs) by utilizing the iPS cell technology. When iPSCs are produced from antigen specific T cells, the rearranged configurations of T cell receptor (TCR) genes are inherited to the iPSCs, and when T cells are regenerated from such iPSCs, all of them should come to express the same TCR as the original one. Therefore it will become possible to obtain de novo generated tumor specific CTLs almost unlimitedly. In line with this concept, we have succeeded in regenerating MART-1 specific T cells (Vizcardo et al, Cell Stem Cell, 2013).
Methods
We firstly established iPSCs from CTLs specific for WT1, expanded from healthy volunteers. CD4/8 DP cells were generated by culturing these T-iPSCs on Op9/DLL1 cells. By stimulating these DP cells by agonist peptide or anti CD3 Ab, CD8 T cells expressing CD8 alpha-beta heterodimers were formed. They can be expanded more than ten thousand fold by repeated TCR stimulation.
Results
Regenerated CD8 T cells exhibited very high antigen specific killing activity comparable to the original CTLs and were able to kill some leukemia cell lines and primaly leukemia cells which express endogenous WT1 protein and HLA A2402. In in vivo leukemia treatment model regenerated CD8 T cells elongated the survival of treated mice.
Conclusion
We have succeded in regenerating CD8 T cells with high antigen specific cytotoxic activity. This method could bring about a breakthrough in cancer immuno-therapy.
Session topic: Gene therapy, cellular immunotherapy and vaccination
Keyword(s): Adoptive immunotherapy, WT1
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Hall C14
Background
Current cancer immunotherapies mainly aim to activate and expand tumor antigen specific cytotoxic T lymphocytes (CTLs) in vitro or in vivo, but these methods are not so successuful because of the difficulty in preparing sufficient number of CTLs.
Aims
For successful cancer immunotherapy, we are trying to expand tumor antigen specific cytotoxic T lymphocytes (CTLs) by utilizing the iPS cell technology. When iPSCs are produced from antigen specific T cells, the rearranged configurations of T cell receptor (TCR) genes are inherited to the iPSCs, and when T cells are regenerated from such iPSCs, all of them should come to express the same TCR as the original one. Therefore it will become possible to obtain de novo generated tumor specific CTLs almost unlimitedly. In line with this concept, we have succeeded in regenerating MART-1 specific T cells (Vizcardo et al, Cell Stem Cell, 2013).
Methods
We firstly established iPSCs from CTLs specific for WT1, expanded from healthy volunteers. CD4/8 DP cells were generated by culturing these T-iPSCs on Op9/DLL1 cells. By stimulating these DP cells by agonist peptide or anti CD3 Ab, CD8 T cells expressing CD8 alpha-beta heterodimers were formed. They can be expanded more than ten thousand fold by repeated TCR stimulation.
Results
Regenerated CD8 T cells exhibited very high antigen specific killing activity comparable to the original CTLs and were able to kill some leukemia cell lines and primaly leukemia cells which express endogenous WT1 protein and HLA A2402. In in vivo leukemia treatment model regenerated CD8 T cells elongated the survival of treated mice.
Conclusion
We have succeded in regenerating CD8 T cells with high antigen specific cytotoxic activity. This method could bring about a breakthrough in cancer immuno-therapy.
Session topic: Gene therapy, cellular immunotherapy and vaccination
Keyword(s): Adoptive immunotherapy, WT1
Abstract: S513
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Hall C14
Background
Current cancer immunotherapies mainly aim to activate and expand tumor antigen specific cytotoxic T lymphocytes (CTLs) in vitro or in vivo, but these methods are not so successuful because of the difficulty in preparing sufficient number of CTLs.
Aims
For successful cancer immunotherapy, we are trying to expand tumor antigen specific cytotoxic T lymphocytes (CTLs) by utilizing the iPS cell technology. When iPSCs are produced from antigen specific T cells, the rearranged configurations of T cell receptor (TCR) genes are inherited to the iPSCs, and when T cells are regenerated from such iPSCs, all of them should come to express the same TCR as the original one. Therefore it will become possible to obtain de novo generated tumor specific CTLs almost unlimitedly. In line with this concept, we have succeeded in regenerating MART-1 specific T cells (Vizcardo et al, Cell Stem Cell, 2013).
Methods
We firstly established iPSCs from CTLs specific for WT1, expanded from healthy volunteers. CD4/8 DP cells were generated by culturing these T-iPSCs on Op9/DLL1 cells. By stimulating these DP cells by agonist peptide or anti CD3 Ab, CD8 T cells expressing CD8 alpha-beta heterodimers were formed. They can be expanded more than ten thousand fold by repeated TCR stimulation.
Results
Regenerated CD8 T cells exhibited very high antigen specific killing activity comparable to the original CTLs and were able to kill some leukemia cell lines and primaly leukemia cells which express endogenous WT1 protein and HLA A2402. In in vivo leukemia treatment model regenerated CD8 T cells elongated the survival of treated mice.
Conclusion
We have succeded in regenerating CD8 T cells with high antigen specific cytotoxic activity. This method could bring about a breakthrough in cancer immuno-therapy.
Session topic: Gene therapy, cellular immunotherapy and vaccination
Keyword(s): Adoptive immunotherapy, WT1
Type: Oral Presentation
Presentation during EHA21: On Saturday, June 11, 2016 from 16:30 - 16:45
Location: Hall C14
Background
Current cancer immunotherapies mainly aim to activate and expand tumor antigen specific cytotoxic T lymphocytes (CTLs) in vitro or in vivo, but these methods are not so successuful because of the difficulty in preparing sufficient number of CTLs.
Aims
For successful cancer immunotherapy, we are trying to expand tumor antigen specific cytotoxic T lymphocytes (CTLs) by utilizing the iPS cell technology. When iPSCs are produced from antigen specific T cells, the rearranged configurations of T cell receptor (TCR) genes are inherited to the iPSCs, and when T cells are regenerated from such iPSCs, all of them should come to express the same TCR as the original one. Therefore it will become possible to obtain de novo generated tumor specific CTLs almost unlimitedly. In line with this concept, we have succeeded in regenerating MART-1 specific T cells (Vizcardo et al, Cell Stem Cell, 2013).
Methods
We firstly established iPSCs from CTLs specific for WT1, expanded from healthy volunteers. CD4/8 DP cells were generated by culturing these T-iPSCs on Op9/DLL1 cells. By stimulating these DP cells by agonist peptide or anti CD3 Ab, CD8 T cells expressing CD8 alpha-beta heterodimers were formed. They can be expanded more than ten thousand fold by repeated TCR stimulation.
Results
Regenerated CD8 T cells exhibited very high antigen specific killing activity comparable to the original CTLs and were able to kill some leukemia cell lines and primaly leukemia cells which express endogenous WT1 protein and HLA A2402. In in vivo leukemia treatment model regenerated CD8 T cells elongated the survival of treated mice.
Conclusion
We have succeded in regenerating CD8 T cells with high antigen specific cytotoxic activity. This method could bring about a breakthrough in cancer immuno-therapy.
Session topic: Gene therapy, cellular immunotherapy and vaccination
Keyword(s): Adoptive immunotherapy, WT1
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