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Here we select some of the classical literature in the field of chimeric antigen receptor technology. It is hoped that these reviews and research articles will help you to understand CAR technology quickly and keep up with the cutting edge development of this area.

TRUCKs: the fourth generation of CARs.

Expert opinion on biological therapy 15, no. 8 (2015): 1145-1154.

Chmielewski, Markus, and Hinrich Abken.

Described a fourth generation car design named TRUCKs, which is CAR with inducible release of a transgenic payload.

The basic principles of chimeric antigen receptor design.

Cancer discovery 3, no. 4 (2013): 388-398.

Sadelain, Michel, Renier Brentjens, and Isabelle Rivière.

This review concluded the basic principles of chimeric antigen receptor design.

Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety.

Leukemia 24, no. 6 (2010): 1160-1170.

Hoyos, Valentina, Barbara Savoldo, Concetta Quintarelli, Aruna Mahendravada, Ming Zhang, Juan Vera, Helen E. Heslop, Cliona M. Rooney, Malcolm K. Brenner, and Gianpietro Dotti.

This study introduced a novel CAR-T construct that added a interleukin-15 (IL-15) gene and an inducible caspase-9-based suicide gene (iC9/CAR.19/IL-15) which gets greater numeric expansion upon antigen stimulation and improved antitumor effects in vivo. This is a fourth generation car t design.

In Vivo Persistence, Tumor Localization, and Antitumor Activity of CAR-Engineered T Cells Is Enhanced by Costimulatory Signaling through CD137 (4-1BB)

Cancer research 71, no. 13 (2011): 4617-4627

Song, De-Gang, Qunrui Ye, Carmine Carpenito, Mathilde Poussin, Li-Ping Wang, Chunyan Ji, Mariangela Figini, Carl H. June, George Coukos, and Daniel J. Powell.

Study of the importance of costimulative signaling domain in car t cell therapy. This is the second generation car t design

A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR

Blood 119, no. 24 (2012): 5697-5705.

Torikai, Hiroki, Andreas Reik, Pei-Qi Liu, Yuanyue Zhou, Ling Zhang, Sourindra Maiti, Helen Huls et al.

This work introduced an universal allogeneic TAA-specific CAR-T cells from one donor that might be administered to multiple recipients. This was achieved by genetically editing CD19-specific CAR T cells using the Sleeping Beauty system to stably introduce the CD19-specific CAR with subsequent permanent deletion of α or β TCR chains with designer zinc finger nuclease.

Redirection of genetically engineered CAR-T cells using bifunctional small molecules

Journal of the American Chemical Society 137.8 (2015): 2832-2835.

Kim, Min Soo, Jennifer SY Ma, Hwayoung Yun, Yu Cao, Ji Young Kim, Victor Chi, Danling Wang et al.

This work has a very smart design that use a bispecific small molecule as an adaptor which have the ability of controling car-t cell specificity to target tumor cells. This paper demonstrated a novel therapeutic approach that combines the dose titratability of small molecules with the potency of CAR-T cell therapy.

Chimeric antigen receptor–engineered T cells as oncolytic virus carriers

Molecular Therapy-Oncolytics 2 (2015): 15014.

VanSeggelen, Heather, et al.

A very interesting work that combine Chimeric antigen receptor with oncolytics virus. Use CAR-T cell as a targeting delivery system to deliver oncolytics virus into target tumor cells.

Safe engineering of CAR T cells for adoptive cell therapy of cancer using long-term episomal gene transfer

EMBO molecular medicine (2016): e201505869.

Jin, Chuan, Grammatiki Fotaki, Mohanraj Ramachandran, Berith Nilsson, Magnus Essand, and Di Yu.

This article present a novel episomal and long-term cell engineering technology. It is based on combining a non-integrating lentiviral (NILV) vector, wherein the integrase is mutated, and a scaffold/matrix attachment region (S/MAR) element, which anchors the episomal circularized DNA to the host cell genome without integration. These findings increase the safety level of T-cell engineering and can offer improved safety for engineering of other cell types

The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity.

Cancer immunology research 3, no. 2 (2015): 125-135.

Hudecek, Michael, Daniel Sommermeyer, Paula L. Kosasih, Anne Silva-Benedict, Lingfeng Liu, Christoph Rader, Michael C. Jensen, and Stanley R. Riddell.

This study examining the length and composition of the extracellular spacer domain for CARs that target different cell surface molecules demonstrates that the length of this region can be tailored for optimal CAR function and identifies mutations in immunoglobulin Fc spacers that are necessary to abrogate Fc receptor binding.

Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells

Journal of hematology & oncology 10.1 (2017): 68.

Qin, Le, Yunxin Lai, Ruocong Zhao, Xinru Wei, Jianyu Weng, Peilong Lai, Baiheng Li et al.

This article discussed the importance of non-signaling extracellular modules (the hinge domain) on the expansion and therapeutic efficacy of CARs.

Engineered T cells: the promise and challenges of cancer immunotherapy

Nature reviews cancer 16.9 (2016): 566-581.

Fesnak, Andrew D., Carl H. June, and Bruce L. Levine.

This Review describe some of the most recent and promising advances in engineered T cell therapy with a particular emphasis on what the next generation of T cell therapy is likely to entail. Highlight variours of new chimeric antigen receptor models and concepts.

TRUCKs: the fourth generation of CARs.

Expert opinion on biological therapy 15, no. 8 (2015): 1145-1154.

Chmielewski, Markus, and Hinrich Abken.

Described a fourth generation car design named TRUCKs, which is CAR with inducible release of a transgenic payload.

The basic principles of chimeric antigen receptor design.

Cancer discovery 3, no. 4 (2013): 388-398.

Sadelain, Michel, Renier Brentjens, and Isabelle Rivière.

This review concluded the basic principles of chimeric antigen receptor design.

Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety.

Leukemia 24, no. 6 (2010): 1160-1170.

Hoyos, Valentina, Barbara Savoldo, Concetta Quintarelli, Aruna Mahendravada, Ming Zhang, Juan Vera, Helen E. Heslop, Cliona M. Rooney, Malcolm K. Brenner, and Gianpietro Dotti.

This study introduced a novel CAR-T construct that added a interleukin-15 (IL-15) gene and an inducible caspase-9-based suicide gene (iC9/CAR.19/IL-15) which gets greater numeric expansion upon antigen stimulation and improved antitumor effects in vivo. This is a fourth generation car t design.

In Vivo Persistence, Tumor Localization, and Antitumor Activity of CAR-Engineered T Cells Is Enhanced by Costimulatory Signaling through CD137 (4-1BB)

Cancer research 71, no. 13 (2011): 4617-4627

Song, De-Gang, Qunrui Ye, Carmine Carpenito, Mathilde Poussin, Li-Ping Wang, Chunyan Ji, Mariangela Figini, Carl H. June, George Coukos, and Daniel J. Powell.

Study of the importance of costimulative signaling domain in car t cell therapy. This is the second generation car t design

A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR

Blood 119, no. 24 (2012): 5697-5705.

Torikai, Hiroki, Andreas Reik, Pei-Qi Liu, Yuanyue Zhou, Ling Zhang, Sourindra Maiti, Helen Huls et al.

This work introduced an universal allogeneic TAA-specific CAR-T cells from one donor that might be administered to multiple recipients. This was achieved by genetically editing CD19-specific CAR T cells using the Sleeping Beauty system to stably introduce the CD19-specific CAR with subsequent permanent deletion of α or β TCR chains with designer zinc finger nuclease.

Redirection of genetically engineered CAR-T cells using bifunctional small molecules

Journal of the American Chemical Society 137.8 (2015): 2832-2835.

Kim, Min Soo, Jennifer SY Ma, Hwayoung Yun, Yu Cao, Ji Young Kim, Victor Chi, Danling Wang et al.

This work has a very smart design that use a bispecific small molecule as an adaptor which have the ability of controling car-t cell specificity to target tumor cells. This paper demonstrated a novel therapeutic approach that combines the dose titratability of small molecules with the potency of CAR-T cell therapy.

Chimeric antigen receptor–engineered T cells as oncolytic virus carriers

Molecular Therapy-Oncolytics 2 (2015): 15014.

VanSeggelen, Heather, et al.

A very interesting work that combine Chimeric antigen receptor with oncolytics virus. Use CAR-T cell as a targeting delivery system to deliver oncolytics virus into target tumor cells.

Safe engineering of CAR T cells for adoptive cell therapy of cancer using long-term episomal gene transfer

EMBO molecular medicine (2016): e201505869.

Jin, Chuan, Grammatiki Fotaki, Mohanraj Ramachandran, Berith Nilsson, Magnus Essand, and Di Yu.

This article present a novel episomal and long-term cell engineering technology. It is based on combining a non-integrating lentiviral (NILV) vector, wherein the integrase is mutated, and a scaffold/matrix attachment region (S/MAR) element, which anchors the episomal circularized DNA to the host cell genome without integration. These findings increase the safety level of T-cell engineering and can offer improved safety for engineering of other cell types

The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity.

Cancer immunology research 3, no. 2 (2015): 125-135.

Hudecek, Michael, Daniel Sommermeyer, Paula L. Kosasih, Anne Silva-Benedict, Lingfeng Liu, Christoph Rader, Michael C. Jensen, and Stanley R. Riddell.

This study examining the length and composition of the extracellular spacer domain for CARs that target different cell surface molecules demonstrates that the length of this region can be tailored for optimal CAR function and identifies mutations in immunoglobulin Fc spacers that are necessary to abrogate Fc receptor binding.

Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells

Journal of hematology & oncology 10.1 (2017): 68.

Qin, Le, Yunxin Lai, Ruocong Zhao, Xinru Wei, Jianyu Weng, Peilong Lai, Baiheng Li et al.

This article discussed the importance of non-signaling extracellular modules (the hinge domain) on the expansion and therapeutic efficacy of CARs.

Engineered T cells: the promise and challenges of cancer immunotherapy

Nature reviews cancer 16.9 (2016): 566-581.

Fesnak, Andrew D., Carl H. June, and Bruce L. Levine.

This Review describe some of the most recent and promising advances in engineered T cell therapy with a particular emphasis on what the next generation of T cell therapy is likely to entail. Highlight variours of new chimeric antigen receptor models and concepts.

TRUCKs: the fourth generation of CARs.

Expert opinion on biological therapy 15, no. 8 (2015): 1145-1154.

Chmielewski, Markus, and Hinrich Abken.

Described a fourth generation car design named TRUCKs, which is CAR with inducible release of a transgenic payload.

The basic principles of chimeric antigen receptor design.

Cancer discovery 3, no. 4 (2013): 388-398.

Sadelain, Michel, Renier Brentjens, and Isabelle Rivière.

This review concluded the basic principles of chimeric antigen receptor design.

Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety.

Leukemia 24, no. 6 (2010): 1160-1170.

Hoyos, Valentina, Barbara Savoldo, Concetta Quintarelli, Aruna Mahendravada, Ming Zhang, Juan Vera, Helen E. Heslop, Cliona M. Rooney, Malcolm K. Brenner, and Gianpietro Dotti.

This study introduced a novel CAR-T construct that added a interleukin-15 (IL-15) gene and an inducible caspase-9-based suicide gene (iC9/CAR.19/IL-15) which gets greater numeric expansion upon antigen stimulation and improved antitumor effects in vivo. This is a fourth generation car t design.

In Vivo Persistence, Tumor Localization, and Antitumor Activity of CAR-Engineered T Cells Is Enhanced by Costimulatory Signaling through CD137 (4-1BB)

Cancer research 71, no. 13 (2011): 4617-4627

Song, De-Gang, Qunrui Ye, Carmine Carpenito, Mathilde Poussin, Li-Ping Wang, Chunyan Ji, Mariangela Figini, Carl H. June, George Coukos, and Daniel J. Powell.

Study of the importance of costimulative signaling domain in car t cell therapy. This is the second generation car t design

A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR

Blood 119, no. 24 (2012): 5697-5705.

Torikai, Hiroki, Andreas Reik, Pei-Qi Liu, Yuanyue Zhou, Ling Zhang, Sourindra Maiti, Helen Huls et al.

This work introduced an universal allogeneic TAA-specific CAR-T cells from one donor that might be administered to multiple recipients. This was achieved by genetically editing CD19-specific CAR T cells using the Sleeping Beauty system to stably introduce the CD19-specific CAR with subsequent permanent deletion of α or β TCR chains with designer zinc finger nuclease.

Redirection of genetically engineered CAR-T cells using bifunctional small molecules

Journal of the American Chemical Society 137.8 (2015): 2832-2835.

Kim, Min Soo, Jennifer SY Ma, Hwayoung Yun, Yu Cao, Ji Young Kim, Victor Chi, Danling Wang et al.

This work has a very smart design that use a bispecific small molecule as an adaptor which have the ability of controling car-t cell specificity to target tumor cells. This paper demonstrated a novel therapeutic approach that combines the dose titratability of small molecules with the potency of CAR-T cell therapy.

Chimeric antigen receptor–engineered T cells as oncolytic virus carriers

Molecular Therapy-Oncolytics 2 (2015): 15014.

VanSeggelen, Heather, et al.

A very interesting work that combine Chimeric antigen receptor with oncolytics virus. Use CAR-T cell as a targeting delivery system to deliver oncolytics virus into target tumor cells.

Safe engineering of CAR T cells for adoptive cell therapy of cancer using long-term episomal gene transfer

EMBO molecular medicine (2016): e201505869.

Jin, Chuan, Grammatiki Fotaki, Mohanraj Ramachandran, Berith Nilsson, Magnus Essand, and Di Yu.

This article present a novel episomal and long-term cell engineering technology. It is based on combining a non-integrating lentiviral (NILV) vector, wherein the integrase is mutated, and a scaffold/matrix attachment region (S/MAR) element, which anchors the episomal circularized DNA to the host cell genome without integration. These findings increase the safety level of T-cell engineering and can offer improved safety for engineering of other cell types

The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity.

Cancer immunology research 3, no. 2 (2015): 125-135.

Hudecek, Michael, Daniel Sommermeyer, Paula L. Kosasih, Anne Silva-Benedict, Lingfeng Liu, Christoph Rader, Michael C. Jensen, and Stanley R. Riddell.

This study examining the length and composition of the extracellular spacer domain for CARs that target different cell surface molecules demonstrates that the length of this region can be tailored for optimal CAR function and identifies mutations in immunoglobulin Fc spacers that are necessary to abrogate Fc receptor binding.

Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells

Journal of hematology & oncology 10.1 (2017): 68.

Qin, Le, Yunxin Lai, Ruocong Zhao, Xinru Wei, Jianyu Weng, Peilong Lai, Baiheng Li et al.

This article discussed the importance of non-signaling extracellular modules (the hinge domain) on the expansion and therapeutic efficacy of CARs.

Engineered T cells: the promise and challenges of cancer immunotherapy

Nature reviews cancer 16.9 (2016): 566-581.

Fesnak, Andrew D., Carl H. June, and Bruce L. Levine.

This Review describe some of the most recent and promising advances in engineered T cell therapy with a particular emphasis on what the next generation of T cell therapy is likely to entail. Highlight variours of new chimeric antigen receptor models and concepts.

TRUCKs: the fourth generation of CARs.

Expert opinion on biological therapy 15, no. 8 (2015): 1145-1154.

Chmielewski, Markus, and Hinrich Abken.

Described a fourth generation car design named TRUCKs, which is CAR with inducible release of a transgenic payload.

The basic principles of chimeric antigen receptor design.

Cancer discovery 3, no. 4 (2013): 388-398.

Sadelain, Michel, Renier Brentjens, and Isabelle Rivière.

This review concluded the basic principles of chimeric antigen receptor design.

Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety.

Leukemia 24, no. 6 (2010): 1160-1170.

Hoyos, Valentina, Barbara Savoldo, Concetta Quintarelli, Aruna Mahendravada, Ming Zhang, Juan Vera, Helen E. Heslop, Cliona M. Rooney, Malcolm K. Brenner, and Gianpietro Dotti.

This study introduced a novel CAR-T construct that added a interleukin-15 (IL-15) gene and an inducible caspase-9-based suicide gene (iC9/CAR.19/IL-15) which gets greater numeric expansion upon antigen stimulation and improved antitumor effects in vivo. This is a fourth generation car t design.

In Vivo Persistence, Tumor Localization, and Antitumor Activity of CAR-Engineered T Cells Is Enhanced by Costimulatory Signaling through CD137 (4-1BB)

Cancer research 71, no. 13 (2011): 4617-4627

Song, De-Gang, Qunrui Ye, Carmine Carpenito, Mathilde Poussin, Li-Ping Wang, Chunyan Ji, Mariangela Figini, Carl H. June, George Coukos, and Daniel J. Powell.

Study of the importance of costimulative signaling domain in car t cell therapy. This is the second generation car t design

A foundation for universal T-cell based immunotherapy: T cells engineered to express a CD19-specific chimeric-antigen-receptor and eliminate expression of endogenous TCR

Blood 119, no. 24 (2012): 5697-5705.

Torikai, Hiroki, Andreas Reik, Pei-Qi Liu, Yuanyue Zhou, Ling Zhang, Sourindra Maiti, Helen Huls et al.

This work introduced an universal allogeneic TAA-specific CAR-T cells from one donor that might be administered to multiple recipients. This was achieved by genetically editing CD19-specific CAR T cells using the Sleeping Beauty system to stably introduce the CD19-specific CAR with subsequent permanent deletion of α or β TCR chains with designer zinc finger nuclease.

Redirection of genetically engineered CAR-T cells using bifunctional small molecules

Journal of the American Chemical Society 137.8 (2015): 2832-2835.

Kim, Min Soo, Jennifer SY Ma, Hwayoung Yun, Yu Cao, Ji Young Kim, Victor Chi, Danling Wang et al.

This work has a very smart design that use a bispecific small molecule as an adaptor which have the ability of controling car-t cell specificity to target tumor cells. This paper demonstrated a novel therapeutic approach that combines the dose titratability of small molecules with the potency of CAR-T cell therapy.

Chimeric antigen receptor–engineered T cells as oncolytic virus carriers

Molecular Therapy-Oncolytics 2 (2015): 15014.

VanSeggelen, Heather, et al.

A very interesting work that combine Chimeric antigen receptor with oncolytics virus. Use CAR-T cell as a targeting delivery system to deliver oncolytics virus into target tumor cells.

Safe engineering of CAR T cells for adoptive cell therapy of cancer using long-term episomal gene transfer

EMBO molecular medicine (2016): e201505869.

Jin, Chuan, Grammatiki Fotaki, Mohanraj Ramachandran, Berith Nilsson, Magnus Essand, and Di Yu.

This article present a novel episomal and long-term cell engineering technology. It is based on combining a non-integrating lentiviral (NILV) vector, wherein the integrase is mutated, and a scaffold/matrix attachment region (S/MAR) element, which anchors the episomal circularized DNA to the host cell genome without integration. These findings increase the safety level of T-cell engineering and can offer improved safety for engineering of other cell types

The nonsignaling extracellular spacer domain of chimeric antigen receptors is decisive for in vivo antitumor activity.

Cancer immunology research 3, no. 2 (2015): 125-135.

Hudecek, Michael, Daniel Sommermeyer, Paula L. Kosasih, Anne Silva-Benedict, Lingfeng Liu, Christoph Rader, Michael C. Jensen, and Stanley R. Riddell.

This study examining the length and composition of the extracellular spacer domain for CARs that target different cell surface molecules demonstrates that the length of this region can be tailored for optimal CAR function and identifies mutations in immunoglobulin Fc spacers that are necessary to abrogate Fc receptor binding.

Incorporation of a hinge domain improves the expansion of chimeric antigen receptor T cells

Journal of hematology & oncology 10.1 (2017): 68.

Qin, Le, Yunxin Lai, Ruocong Zhao, Xinru Wei, Jianyu Weng, Peilong Lai, Baiheng Li et al.

This article discussed the importance of non-signaling extracellular modules (the hinge domain) on the expansion and therapeutic efficacy of CARs.

Engineered T cells: the promise and challenges of cancer immunotherapy

Nature reviews cancer 16.9 (2016): 566-581.

Fesnak, Andrew D., Carl H. June, and Bruce L. Levine.

This Review describe some of the most recent and promising advances in engineered T cell therapy with a particular emphasis on what the next generation of T cell therapy is likely to entail. Highlight variours of new chimeric antigen receptor models and concepts.


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