Driving gene-engineered T cell immunotherapy of cancer
Chimeric antigen receptor （CAR） gene-engineered T cell therapy holds the potential to make a meaningful differ- ence in the lives of patients with terminal cancers. For decades, cancer therapy was based on biophysical parameters, with surgical resection to debulk, followed by radiation and chemother...
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| Published in | Cell research Vol. 27; no. 1; pp. 38 - 58 |
|---|---|
| Main Authors | , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
01.01.2017
Nature Publishing Group |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1001-0602 1748-7838 1748-7838 |
| DOI | 10.1038/cr.2016.154 |
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| Abstract | Chimeric antigen receptor （CAR） gene-engineered T cell therapy holds the potential to make a meaningful differ- ence in the lives of patients with terminal cancers. For decades, cancer therapy was based on biophysical parameters, with surgical resection to debulk, followed by radiation and chemotherapy to target the rapidly growing tumor cells, while mostly sparing quiescent normal tissues. One breakthrough occurred with allogeneic bone-marrow transplant for patients with leukemia, which provided a sometimes curative therapy. The field of adoptive cell therapy for sol- id tumors was established with the discovery that tumor-infiltrating lymphocytes could be expanded and used to treat and even cure patients with metastatic melanoma. Tumor-specific T-cell receptors （TCRs） were identified and engineered into patient peripheral blood lymphocytes, which were also found to treat tumors. However, these were limited by patient HLA-restriction. Close behind came generation of CAR, combining the exquisite recognition of an antibody with the effector function of a T cell. The advent of CD19-targeted CARs for treating patients with multiple forms of advanced B-cell malignancies met with great success, with up to 95% response rates. Applying CAR treat- ment to solid tumors, however, has just begun, but already certain factors have been made clear： the tumor target is of utmost importance for clinicians to do no harm; and solid tumors respond differently to CAR therapy compared with hematologic ones. Here we review the state of clinical gene-engineered T cell immunotherapy, its successes, chal- lenges, and future. |
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| AbstractList | Chimeric antigen receptor (CAR) gene-engineered T cell therapy holds the potential to make a meaningful difference in the lives of patients with terminal cancers. For decades, cancer therapy was based on biophysical parameters, with surgical resection to debulk, followed by radiation and chemotherapy to target the rapidly growing tumor cells, while mostly sparing quiescent normal tissues. One breakthrough occurred with allogeneic bone-marrow transplant for patients with leukemia, which provided a sometimes curative therapy. The field of adoptive cell therapy for solid tumors was established with the discovery that tumor-infiltrating lymphocytes could be expanded and used to treat and even cure patients with metastatic melanoma. Tumor-specific T-cell receptors (TCRs) were identified and engineered into patient peripheral blood lymphocytes, which were also found to treat tumors. However, these were limited by patient HLA-restriction. Close behind came generation of CAR, combining the exquisite recognition of an antibody with the effector function of a T cell. The advent of CD19-targeted CARs for treating patients with multiple forms of advanced B-cell malignancies met with great success, with up to 95% response rates. Applying CAR treatment to solid tumors, however, has just begun, but already certain factors have been made clear: the tumor target is of utmost importance for clinicians to do no harm; and solid tumors respond differently to CAR therapy compared with hematologic ones. Here we review the state of clinical gene-engineered T cell immunotherapy, its successes, challenges, and future.Chimeric antigen receptor (CAR) gene-engineered T cell therapy holds the potential to make a meaningful difference in the lives of patients with terminal cancers. For decades, cancer therapy was based on biophysical parameters, with surgical resection to debulk, followed by radiation and chemotherapy to target the rapidly growing tumor cells, while mostly sparing quiescent normal tissues. One breakthrough occurred with allogeneic bone-marrow transplant for patients with leukemia, which provided a sometimes curative therapy. The field of adoptive cell therapy for solid tumors was established with the discovery that tumor-infiltrating lymphocytes could be expanded and used to treat and even cure patients with metastatic melanoma. Tumor-specific T-cell receptors (TCRs) were identified and engineered into patient peripheral blood lymphocytes, which were also found to treat tumors. However, these were limited by patient HLA-restriction. Close behind came generation of CAR, combining the exquisite recognition of an antibody with the effector function of a T cell. The advent of CD19-targeted CARs for treating patients with multiple forms of advanced B-cell malignancies met with great success, with up to 95% response rates. Applying CAR treatment to solid tumors, however, has just begun, but already certain factors have been made clear: the tumor target is of utmost importance for clinicians to do no harm; and solid tumors respond differently to CAR therapy compared with hematologic ones. Here we review the state of clinical gene-engineered T cell immunotherapy, its successes, challenges, and future. Chimeric antigen receptor (CAR) gene-engineered T cell therapy holds the potential to make a meaningful difference in the lives of patients with terminal cancers. For decades, cancer therapy was based on biophysical parameters, with surgical resection to debulk, followed by radiation and chemotherapy to target the rapidly growing tumor cells, while mostly sparing quiescent normal tissues. One breakthrough occurred with allogeneic bone-marrow transplant for patients with leukemia, which provided a sometimes curative therapy. The field of adoptive cell therapy for solid tumors was established with the discovery that tumor-infiltrating lymphocytes could be expanded and used to treat and even cure patients with metastatic melanoma. Tumor-specific T-cell receptors (TCRs) were identified and engineered into patient peripheral blood lymphocytes, which were also found to treat tumors. However, these were limited by patient HLA-restriction. Close behind came generation of CAR, combining the exquisite recognition of an antibody with the effector function of a T cell. The advent of CD19-targeted CARs for treating patients with multiple forms of advanced B-cell malignancies met with great success, with up to 95% response rates. Applying CAR treatment to solid tumors, however, has just begun, but already certain factors have been made clear: the tumor target is of utmost importance for clinicians to do no harm; and solid tumors respond differently to CAR therapy compared with hematologic ones. Here we review the state of clinical gene-engineered T cell immunotherapy, its successes, challenges, and future. Chimeric antigen receptor （CAR） gene-engineered T cell therapy holds the potential to make a meaningful differ- ence in the lives of patients with terminal cancers. For decades, cancer therapy was based on biophysical parameters, with surgical resection to debulk, followed by radiation and chemotherapy to target the rapidly growing tumor cells, while mostly sparing quiescent normal tissues. One breakthrough occurred with allogeneic bone-marrow transplant for patients with leukemia, which provided a sometimes curative therapy. The field of adoptive cell therapy for sol- id tumors was established with the discovery that tumor-infiltrating lymphocytes could be expanded and used to treat and even cure patients with metastatic melanoma. Tumor-specific T-cell receptors （TCRs） were identified and engineered into patient peripheral blood lymphocytes, which were also found to treat tumors. However, these were limited by patient HLA-restriction. Close behind came generation of CAR, combining the exquisite recognition of an antibody with the effector function of a T cell. The advent of CD19-targeted CARs for treating patients with multiple forms of advanced B-cell malignancies met with great success, with up to 95% response rates. Applying CAR treat- ment to solid tumors, however, has just begun, but already certain factors have been made clear： the tumor target is of utmost importance for clinicians to do no harm; and solid tumors respond differently to CAR therapy compared with hematologic ones. Here we review the state of clinical gene-engineered T cell immunotherapy, its successes, chal- lenges, and future. |
| Author | Laura A Johnson Carl H June |
| AuthorAffiliation | Center for CelIuIar Immunotherapies, PereIman School of Medicine, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA |
| Author_xml | – sequence: 1 givenname: Laura A surname: Johnson fullname: Johnson, Laura A email: ljohnso@upenn.edu organization: Department of Pathology and Laboratory Medicine, Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania – sequence: 2 givenname: Carl H surname: June fullname: June, Carl H email: cjune@upenn.edu organization: Department of Pathology and Laboratory Medicine, Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28025979$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences 2017 Copyright Nature Publishing Group Jan 2017 Copyright © 2017 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences 2017 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences |
| Copyright_xml | – notice: Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences 2017 – notice: Copyright Nature Publishing Group Jan 2017 – notice: Copyright © 2017 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences 2017 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences |
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| DOI | 10.1038/cr.2016.154 |
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| Keywords | CD19 chimeric antigen receptor T cell immunotherapy |
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| Notes | 31-1568 chimeric antigen receptor; T cell immunotherapy; CD 19 Chimeric antigen receptor （CAR） gene-engineered T cell therapy holds the potential to make a meaningful differ- ence in the lives of patients with terminal cancers. For decades, cancer therapy was based on biophysical parameters, with surgical resection to debulk, followed by radiation and chemotherapy to target the rapidly growing tumor cells, while mostly sparing quiescent normal tissues. One breakthrough occurred with allogeneic bone-marrow transplant for patients with leukemia, which provided a sometimes curative therapy. The field of adoptive cell therapy for sol- id tumors was established with the discovery that tumor-infiltrating lymphocytes could be expanded and used to treat and even cure patients with metastatic melanoma. Tumor-specific T-cell receptors （TCRs） were identified and engineered into patient peripheral blood lymphocytes, which were also found to treat tumors. However, these were limited by patient HLA-restriction. Close behind came generation of CAR, combining the exquisite recognition of an antibody with the effector function of a T cell. The advent of CD19-targeted CARs for treating patients with multiple forms of advanced B-cell malignancies met with great success, with up to 95% response rates. Applying CAR treat- ment to solid tumors, however, has just begun, but already certain factors have been made clear： the tumor target is of utmost importance for clinicians to do no harm; and solid tumors respond differently to CAR therapy compared with hematologic ones. Here we review the state of clinical gene-engineered T cell immunotherapy, its successes, chal- lenges, and future. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23 |
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| PublicationTitle | Cell research |
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| Snippet | Chimeric antigen receptor （CAR） gene-engineered T cell therapy holds the potential to make a meaningful differ- ence in the lives of patients with terminal... Chimeric antigen receptor (CAR) gene-engineered T cell therapy holds the potential to make a meaningful difference in the lives of patients with terminal... |
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| SubjectTerms | 631/1647/1511 631/250/1619/554 631/250/580 692/699/67/1059/2325 Biomedical and Life Sciences Bone marrow Cell Biology Clinical Trials as Topic Genetic Engineering Haplotypes - genetics Humans Immunotherapy Leukemia Life Sciences Lymphocytes Melanoma Neoplasms - immunology Neoplasms - therapy Review T-Lymphocytes - immunology Tumors T细胞受体 人外周血淋巴细胞 免疫治疗 基因工程 生物物理参数 癌症患者 肿瘤细胞 驱动 |
| Title | Driving gene-engineered T cell immunotherapy of cancer |
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