Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1

Abstract T cell receptor (TCR) gene-engineered T cells have shown promise in the treatment of melanoma and synovial cell sarcoma, but their application to epithelial cancers has been limited. The identification of novel therapeutic TCRs for the targeting of these tumors is important for the developm...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Marcinkowski, Bridget [verfasserIn] Stevanović, Sanja Helman, Sarah R. Norberg, Scott M. Serna, Carylinda Jin, Benjamin Gkitsas, Nikolaos Kadakia, Tejas Warner, Andrew Davis, Jeremy L. Rooper, Lisa Hinrichs, Christian S.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Gastric cancer Breast cancer KK-LC-1 Cell therapy Gene therapy T cell receptor CAR-T Gene engineering T cell Immunotherapy

Anmerkung:	© The Author(s). 2019

Übergeordnetes Werk:	Enthalten in: Journal for ImmunoTherapy of Cancer - London : BioMed Central, 2013, 7(2019), 1 vom: 28. Aug.
Übergeordnetes Werk:	volume:7 ; year:2019 ; number:1 ; day:28 ; month:08

Links:	Volltext

DOI / URN:	10.1186/s40425-019-0678-x

Katalog-ID:	SPR036440434

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allfields	10.1186/s40425-019-0678-x doi (DE-627)SPR036440434 (SPR)s40425-019-0678-x-e DE-627 ger DE-627 rakwb eng Marcinkowski, Bridget verfasserin aut Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Abstract T cell receptor (TCR) gene-engineered T cells have shown promise in the treatment of melanoma and synovial cell sarcoma, but their application to epithelial cancers has been limited. The identification of novel therapeutic TCRs for the targeting of these tumors is important for the development of new treatments. Here, we describe the preclinical characterization of a TCR directed against Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1, encoded by CT83), a cancer germline antigen with frequent expression in human epithelial malignancies including gastric cancer, breast cancer, and lung cancer. Gene-engineered T cells expressing the KK-LC-1 TCR (KK-LC-1 TCR-Ts) demonstrated recognition of CT83+ tumor lines in vitro and mediated regression of established CT83+ xenograft tumors in immunodeficient mouse models. Cross-reactivity studies based on experimental determination of the recognition motifs for the target epitope did not demonstrate cross-reactivity against other human proteins. CT83 gene expression studies in 51 non-neural tissues and 24 neural tissues showed expression restricted exclusively to germ cells. CT83 was however expressed by a range of epithelial cancers, with the highest expression noted in gastric cancer. Collectively, these findings support the further investigation and clinical testing of KK-LC-1 TCR-Ts for gastric cancer and possibly other malignancies. Gastric cancer (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 KK-LC-1 (dpeaa)DE-He213 Cell therapy (dpeaa)DE-He213 Gene therapy (dpeaa)DE-He213 T cell receptor (dpeaa)DE-He213 CAR-T (dpeaa)DE-He213 Gene engineering (dpeaa)DE-He213 T cell (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Stevanović, Sanja aut Helman, Sarah R. aut Norberg, Scott M. aut Serna, Carylinda aut Jin, Benjamin aut Gkitsas, Nikolaos aut Kadakia, Tejas aut Warner, Andrew aut Davis, Jeremy L. aut Rooper, Lisa aut Hinrichs, Christian S. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 7(2019), 1 vom: 28. Aug. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:7 year:2019 number:1 day:28 month:08 https://dx.doi.org/10.1186/s40425-019-0678-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019 1 28 08
spelling	10.1186/s40425-019-0678-x doi (DE-627)SPR036440434 (SPR)s40425-019-0678-x-e DE-627 ger DE-627 rakwb eng Marcinkowski, Bridget verfasserin aut Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Abstract T cell receptor (TCR) gene-engineered T cells have shown promise in the treatment of melanoma and synovial cell sarcoma, but their application to epithelial cancers has been limited. The identification of novel therapeutic TCRs for the targeting of these tumors is important for the development of new treatments. Here, we describe the preclinical characterization of a TCR directed against Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1, encoded by CT83), a cancer germline antigen with frequent expression in human epithelial malignancies including gastric cancer, breast cancer, and lung cancer. Gene-engineered T cells expressing the KK-LC-1 TCR (KK-LC-1 TCR-Ts) demonstrated recognition of CT83+ tumor lines in vitro and mediated regression of established CT83+ xenograft tumors in immunodeficient mouse models. Cross-reactivity studies based on experimental determination of the recognition motifs for the target epitope did not demonstrate cross-reactivity against other human proteins. CT83 gene expression studies in 51 non-neural tissues and 24 neural tissues showed expression restricted exclusively to germ cells. CT83 was however expressed by a range of epithelial cancers, with the highest expression noted in gastric cancer. Collectively, these findings support the further investigation and clinical testing of KK-LC-1 TCR-Ts for gastric cancer and possibly other malignancies. Gastric cancer (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 KK-LC-1 (dpeaa)DE-He213 Cell therapy (dpeaa)DE-He213 Gene therapy (dpeaa)DE-He213 T cell receptor (dpeaa)DE-He213 CAR-T (dpeaa)DE-He213 Gene engineering (dpeaa)DE-He213 T cell (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Stevanović, Sanja aut Helman, Sarah R. aut Norberg, Scott M. aut Serna, Carylinda aut Jin, Benjamin aut Gkitsas, Nikolaos aut Kadakia, Tejas aut Warner, Andrew aut Davis, Jeremy L. aut Rooper, Lisa aut Hinrichs, Christian S. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 7(2019), 1 vom: 28. Aug. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:7 year:2019 number:1 day:28 month:08 https://dx.doi.org/10.1186/s40425-019-0678-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019 1 28 08
allfields_unstemmed	10.1186/s40425-019-0678-x doi (DE-627)SPR036440434 (SPR)s40425-019-0678-x-e DE-627 ger DE-627 rakwb eng Marcinkowski, Bridget verfasserin aut Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Abstract T cell receptor (TCR) gene-engineered T cells have shown promise in the treatment of melanoma and synovial cell sarcoma, but their application to epithelial cancers has been limited. The identification of novel therapeutic TCRs for the targeting of these tumors is important for the development of new treatments. Here, we describe the preclinical characterization of a TCR directed against Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1, encoded by CT83), a cancer germline antigen with frequent expression in human epithelial malignancies including gastric cancer, breast cancer, and lung cancer. Gene-engineered T cells expressing the KK-LC-1 TCR (KK-LC-1 TCR-Ts) demonstrated recognition of CT83+ tumor lines in vitro and mediated regression of established CT83+ xenograft tumors in immunodeficient mouse models. Cross-reactivity studies based on experimental determination of the recognition motifs for the target epitope did not demonstrate cross-reactivity against other human proteins. CT83 gene expression studies in 51 non-neural tissues and 24 neural tissues showed expression restricted exclusively to germ cells. CT83 was however expressed by a range of epithelial cancers, with the highest expression noted in gastric cancer. Collectively, these findings support the further investigation and clinical testing of KK-LC-1 TCR-Ts for gastric cancer and possibly other malignancies. Gastric cancer (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 KK-LC-1 (dpeaa)DE-He213 Cell therapy (dpeaa)DE-He213 Gene therapy (dpeaa)DE-He213 T cell receptor (dpeaa)DE-He213 CAR-T (dpeaa)DE-He213 Gene engineering (dpeaa)DE-He213 T cell (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Stevanović, Sanja aut Helman, Sarah R. aut Norberg, Scott M. aut Serna, Carylinda aut Jin, Benjamin aut Gkitsas, Nikolaos aut Kadakia, Tejas aut Warner, Andrew aut Davis, Jeremy L. aut Rooper, Lisa aut Hinrichs, Christian S. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 7(2019), 1 vom: 28. Aug. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:7 year:2019 number:1 day:28 month:08 https://dx.doi.org/10.1186/s40425-019-0678-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019 1 28 08
allfieldsGer	10.1186/s40425-019-0678-x doi (DE-627)SPR036440434 (SPR)s40425-019-0678-x-e DE-627 ger DE-627 rakwb eng Marcinkowski, Bridget verfasserin aut Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Abstract T cell receptor (TCR) gene-engineered T cells have shown promise in the treatment of melanoma and synovial cell sarcoma, but their application to epithelial cancers has been limited. The identification of novel therapeutic TCRs for the targeting of these tumors is important for the development of new treatments. Here, we describe the preclinical characterization of a TCR directed against Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1, encoded by CT83), a cancer germline antigen with frequent expression in human epithelial malignancies including gastric cancer, breast cancer, and lung cancer. Gene-engineered T cells expressing the KK-LC-1 TCR (KK-LC-1 TCR-Ts) demonstrated recognition of CT83+ tumor lines in vitro and mediated regression of established CT83+ xenograft tumors in immunodeficient mouse models. Cross-reactivity studies based on experimental determination of the recognition motifs for the target epitope did not demonstrate cross-reactivity against other human proteins. CT83 gene expression studies in 51 non-neural tissues and 24 neural tissues showed expression restricted exclusively to germ cells. CT83 was however expressed by a range of epithelial cancers, with the highest expression noted in gastric cancer. Collectively, these findings support the further investigation and clinical testing of KK-LC-1 TCR-Ts for gastric cancer and possibly other malignancies. Gastric cancer (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 KK-LC-1 (dpeaa)DE-He213 Cell therapy (dpeaa)DE-He213 Gene therapy (dpeaa)DE-He213 T cell receptor (dpeaa)DE-He213 CAR-T (dpeaa)DE-He213 Gene engineering (dpeaa)DE-He213 T cell (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Stevanović, Sanja aut Helman, Sarah R. aut Norberg, Scott M. aut Serna, Carylinda aut Jin, Benjamin aut Gkitsas, Nikolaos aut Kadakia, Tejas aut Warner, Andrew aut Davis, Jeremy L. aut Rooper, Lisa aut Hinrichs, Christian S. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 7(2019), 1 vom: 28. Aug. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:7 year:2019 number:1 day:28 month:08 https://dx.doi.org/10.1186/s40425-019-0678-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019 1 28 08
allfieldsSound	10.1186/s40425-019-0678-x doi (DE-627)SPR036440434 (SPR)s40425-019-0678-x-e DE-627 ger DE-627 rakwb eng Marcinkowski, Bridget verfasserin aut Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Abstract T cell receptor (TCR) gene-engineered T cells have shown promise in the treatment of melanoma and synovial cell sarcoma, but their application to epithelial cancers has been limited. The identification of novel therapeutic TCRs for the targeting of these tumors is important for the development of new treatments. Here, we describe the preclinical characterization of a TCR directed against Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1, encoded by CT83), a cancer germline antigen with frequent expression in human epithelial malignancies including gastric cancer, breast cancer, and lung cancer. Gene-engineered T cells expressing the KK-LC-1 TCR (KK-LC-1 TCR-Ts) demonstrated recognition of CT83+ tumor lines in vitro and mediated regression of established CT83+ xenograft tumors in immunodeficient mouse models. Cross-reactivity studies based on experimental determination of the recognition motifs for the target epitope did not demonstrate cross-reactivity against other human proteins. CT83 gene expression studies in 51 non-neural tissues and 24 neural tissues showed expression restricted exclusively to germ cells. CT83 was however expressed by a range of epithelial cancers, with the highest expression noted in gastric cancer. Collectively, these findings support the further investigation and clinical testing of KK-LC-1 TCR-Ts for gastric cancer and possibly other malignancies. Gastric cancer (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 KK-LC-1 (dpeaa)DE-He213 Cell therapy (dpeaa)DE-He213 Gene therapy (dpeaa)DE-He213 T cell receptor (dpeaa)DE-He213 CAR-T (dpeaa)DE-He213 Gene engineering (dpeaa)DE-He213 T cell (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213 Stevanović, Sanja aut Helman, Sarah R. aut Norberg, Scott M. aut Serna, Carylinda aut Jin, Benjamin aut Gkitsas, Nikolaos aut Kadakia, Tejas aut Warner, Andrew aut Davis, Jeremy L. aut Rooper, Lisa aut Hinrichs, Christian S. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 7(2019), 1 vom: 28. Aug. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:7 year:2019 number:1 day:28 month:08 https://dx.doi.org/10.1186/s40425-019-0678-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019 1 28 08
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source	Enthalten in Journal for ImmunoTherapy of Cancer 7(2019), 1 vom: 28. Aug. volume:7 year:2019 number:1 day:28 month:08
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topic_facet	Gastric cancer Breast cancer KK-LC-1 Cell therapy Gene therapy T cell receptor CAR-T Gene engineering T cell Immunotherapy
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authorswithroles_txt_mv	Marcinkowski, Bridget @@aut@@ Stevanović, Sanja @@aut@@ Helman, Sarah R. @@aut@@ Norberg, Scott M. @@aut@@ Serna, Carylinda @@aut@@ Jin, Benjamin @@aut@@ Gkitsas, Nikolaos @@aut@@ Kadakia, Tejas @@aut@@ Warner, Andrew @@aut@@ Davis, Jeremy L. @@aut@@ Rooper, Lisa @@aut@@ Hinrichs, Christian S. @@aut@@
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author	Marcinkowski, Bridget
spellingShingle	Marcinkowski, Bridget misc Gastric cancer misc Breast cancer misc KK-LC-1 misc Cell therapy misc Gene therapy misc T cell receptor misc CAR-T misc Gene engineering misc T cell misc Immunotherapy Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1
authorStr	Marcinkowski, Bridget
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topic_title	Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1 Gastric cancer (dpeaa)DE-He213 Breast cancer (dpeaa)DE-He213 KK-LC-1 (dpeaa)DE-He213 Cell therapy (dpeaa)DE-He213 Gene therapy (dpeaa)DE-He213 T cell receptor (dpeaa)DE-He213 CAR-T (dpeaa)DE-He213 Gene engineering (dpeaa)DE-He213 T cell (dpeaa)DE-He213 Immunotherapy (dpeaa)DE-He213
topic	misc Gastric cancer misc Breast cancer misc KK-LC-1 misc Cell therapy misc Gene therapy misc T cell receptor misc CAR-T misc Gene engineering misc T cell misc Immunotherapy
topic_unstemmed	misc Gastric cancer misc Breast cancer misc KK-LC-1 misc Cell therapy misc Gene therapy misc T cell receptor misc CAR-T misc Gene engineering misc T cell misc Immunotherapy
topic_browse	misc Gastric cancer misc Breast cancer misc KK-LC-1 misc Cell therapy misc Gene therapy misc T cell receptor misc CAR-T misc Gene engineering misc T cell misc Immunotherapy
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title	Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1
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title_full	Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1
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author_browse	Marcinkowski, Bridget Stevanović, Sanja Helman, Sarah R. Norberg, Scott M. Serna, Carylinda Jin, Benjamin Gkitsas, Nikolaos Kadakia, Tejas Warner, Andrew Davis, Jeremy L. Rooper, Lisa Hinrichs, Christian S.
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title_sort	cancer targeting by tcr gene-engineered t cells directed against kita-kyushu lung cancer antigen-1
title_auth	Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1
abstract	Abstract T cell receptor (TCR) gene-engineered T cells have shown promise in the treatment of melanoma and synovial cell sarcoma, but their application to epithelial cancers has been limited. The identification of novel therapeutic TCRs for the targeting of these tumors is important for the development of new treatments. Here, we describe the preclinical characterization of a TCR directed against Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1, encoded by CT83), a cancer germline antigen with frequent expression in human epithelial malignancies including gastric cancer, breast cancer, and lung cancer. Gene-engineered T cells expressing the KK-LC-1 TCR (KK-LC-1 TCR-Ts) demonstrated recognition of CT83+ tumor lines in vitro and mediated regression of established CT83+ xenograft tumors in immunodeficient mouse models. Cross-reactivity studies based on experimental determination of the recognition motifs for the target epitope did not demonstrate cross-reactivity against other human proteins. CT83 gene expression studies in 51 non-neural tissues and 24 neural tissues showed expression restricted exclusively to germ cells. CT83 was however expressed by a range of epithelial cancers, with the highest expression noted in gastric cancer. Collectively, these findings support the further investigation and clinical testing of KK-LC-1 TCR-Ts for gastric cancer and possibly other malignancies. © The Author(s). 2019
abstractGer	Abstract T cell receptor (TCR) gene-engineered T cells have shown promise in the treatment of melanoma and synovial cell sarcoma, but their application to epithelial cancers has been limited. The identification of novel therapeutic TCRs for the targeting of these tumors is important for the development of new treatments. Here, we describe the preclinical characterization of a TCR directed against Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1, encoded by CT83), a cancer germline antigen with frequent expression in human epithelial malignancies including gastric cancer, breast cancer, and lung cancer. Gene-engineered T cells expressing the KK-LC-1 TCR (KK-LC-1 TCR-Ts) demonstrated recognition of CT83+ tumor lines in vitro and mediated regression of established CT83+ xenograft tumors in immunodeficient mouse models. Cross-reactivity studies based on experimental determination of the recognition motifs for the target epitope did not demonstrate cross-reactivity against other human proteins. CT83 gene expression studies in 51 non-neural tissues and 24 neural tissues showed expression restricted exclusively to germ cells. CT83 was however expressed by a range of epithelial cancers, with the highest expression noted in gastric cancer. Collectively, these findings support the further investigation and clinical testing of KK-LC-1 TCR-Ts for gastric cancer and possibly other malignancies. © The Author(s). 2019
abstract_unstemmed	Abstract T cell receptor (TCR) gene-engineered T cells have shown promise in the treatment of melanoma and synovial cell sarcoma, but their application to epithelial cancers has been limited. The identification of novel therapeutic TCRs for the targeting of these tumors is important for the development of new treatments. Here, we describe the preclinical characterization of a TCR directed against Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1, encoded by CT83), a cancer germline antigen with frequent expression in human epithelial malignancies including gastric cancer, breast cancer, and lung cancer. Gene-engineered T cells expressing the KK-LC-1 TCR (KK-LC-1 TCR-Ts) demonstrated recognition of CT83+ tumor lines in vitro and mediated regression of established CT83+ xenograft tumors in immunodeficient mouse models. Cross-reactivity studies based on experimental determination of the recognition motifs for the target epitope did not demonstrate cross-reactivity against other human proteins. CT83 gene expression studies in 51 non-neural tissues and 24 neural tissues showed expression restricted exclusively to germ cells. CT83 was however expressed by a range of epithelial cancers, with the highest expression noted in gastric cancer. Collectively, these findings support the further investigation and clinical testing of KK-LC-1 TCR-Ts for gastric cancer and possibly other malignancies. © The Author(s). 2019
collection_details	GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700
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title_short	Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1
url	https://dx.doi.org/10.1186/s40425-019-0678-x
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author2	Stevanović, Sanja Helman, Sarah R. Norberg, Scott M. Serna, Carylinda Jin, Benjamin Gkitsas, Nikolaos Kadakia, Tejas Warner, Andrew Davis, Jeremy L. Rooper, Lisa Hinrichs, Christian S.
author2Str	Stevanović, Sanja Helman, Sarah R. Norberg, Scott M. Serna, Carylinda Jin, Benjamin Gkitsas, Nikolaos Kadakia, Tejas Warner, Andrew Davis, Jeremy L. Rooper, Lisa Hinrichs, Christian S.
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up_date	2024-07-03T17:37:56.166Z
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The identification of novel therapeutic TCRs for the targeting of these tumors is important for the development of new treatments. Here, we describe the preclinical characterization of a TCR directed against Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1, encoded by CT83), a cancer germline antigen with frequent expression in human epithelial malignancies including gastric cancer, breast cancer, and lung cancer. Gene-engineered T cells expressing the KK-LC-1 TCR (KK-LC-1 TCR-Ts) demonstrated recognition of CT83+ tumor lines in vitro and mediated regression of established CT83+ xenograft tumors in immunodeficient mouse models. Cross-reactivity studies based on experimental determination of the recognition motifs for the target epitope did not demonstrate cross-reactivity against other human proteins. CT83 gene expression studies in 51 non-neural tissues and 24 neural tissues showed expression restricted exclusively to germ cells. CT83 was however expressed by a range of epithelial cancers, with the highest expression noted in gastric cancer. 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Cancer targeting by TCR gene-engineered T cells directed against Kita-Kyushu Lung Cancer Antigen-1

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