RapamycinFungusV1, Main, Exploration, bibRecord, 000A86

Human melanoma immunotherapy using tumor antigen-specific T cells generated in humanized mice.

Identifieur interne : 000A86 ( Main/Exploration ); précédent : 000A85; suivant : 000A87

Human melanoma immunotherapy using tumor antigen-specific T cells generated in humanized mice.

Auteurs : Zheng Hu [République populaire de Chine, États-Unis] ; Jinxing Xia [États-Unis] ; Wei Fan [République populaire de Chine] ; Jennifer Wargo [États-Unis] ; Yong-Guang Yang [République populaire de Chine, États-Unis]

Source :

Oncotarget [ 1949-2553 ] ; 2016.

RBID : pubmed:26824989

Descripteurs français

KwdFr :
- Activation des lymphocytes (MeSH), Animaux (MeSH), Antigène HLA-A2 (immunologie), Antigène MART-1 (immunologie), Cellules cultivées (MeSH), Cytotoxicité immunologique (immunologie), Fragments peptidiques (administration et posologie), Fragments peptidiques (pharmacologie), Humains (MeSH), Immunisation (MeSH), Immunothérapie (MeSH), Lymphocytes T CD8+ (immunologie), Lymphocytes T cytotoxiques (immunologie), Mélanome (immunologie), Mélanome (secondaire), Mélanome (thérapie), Souris (MeSH), Souris SCID (MeSH), Souris de lignée NOD (MeSH).
MESH :
- administration et posologie : Fragments peptidiques.
- immunologie : Antigène HLA-A2, Antigène MART-1, Cytotoxicité immunologique, Lymphocytes T CD8+, Lymphocytes T cytotoxiques, Mélanome.
- pharmacologie : Fragments peptidiques.
- secondaire : Mélanome.
- thérapie : Mélanome.
- Activation des lymphocytes, Animaux, Cellules cultivées, Humains, Immunisation, Immunothérapie, Souris, Souris SCID, Souris de lignée NOD.

English descriptors

KwdEn :
- Animals (MeSH), CD8-Positive T-Lymphocytes (immunology), Cells, Cultured (MeSH), Cytotoxicity, Immunologic (immunology), HLA-A2 Antigen (immunology), Humans (MeSH), Immunization (MeSH), Immunotherapy (MeSH), Lymphocyte Activation (MeSH), MART-1 Antigen (immunology), Melanoma (immunology), Melanoma (secondary), Melanoma (therapy), Mice (MeSH), Mice, Inbred NOD (MeSH), Mice, SCID (MeSH), Peptide Fragments (administration & dosage), Peptide Fragments (pharmacology), T-Lymphocytes, Cytotoxic (immunology).
MESH :
- chemical , administration & dosage : Peptide Fragments.
- chemical , immunology : HLA-A2 Antigen, MART-1 Antigen.
- immunology : CD8-Positive T-Lymphocytes, Cytotoxicity, Immunologic, Melanoma, T-Lymphocytes, Cytotoxic.
- chemical , pharmacology : Peptide Fragments.
- secondary : Melanoma.
- therapy : Melanoma.
- Animals, Cells, Cultured, Humans, Immunization, Immunotherapy, Lymphocyte Activation, Mice, Mice, Inbred NOD, Mice, SCID.

Abstract

A major factor hindering the exploration of adoptive immunotherapy in preclinical settings is the limited availability of tumor-reactive human T cells. Here we developed a humanized mouse model that permits large-scale production of human T cells expressing the engineered melanoma antigen MART-1-specific TCR. Humanized mice, made by transplantation of human fetal thymic tissue and CD34+ cells virally-transduced with HLA class I-restricted melanoma antigen (MART-1)-specific TCR gene, showed efficient development of MART-1-TCR+ human T cells with predominantly CD8+ cells. Importantly, MART-1-TCR+CD8+ T cells developing in these mice were capable of mounting antigen-specific responses in vivo, as evidenced by their proliferation, phenotypic conversion and IFN-γ production following MART-1 peptide immunization. Moreover, these MART-1-TCR+CD8+ T cells mediated efficient killing of melanoma cells in an HLA/antigen-dependent manner. Adoptive transfer of in vitro expanded MART-1-TCR+CD8+ T cells induced potent antitumor responses that were further enhanced by IL-15 treatment in melanoma-bearing recipients. Finally, a short incubation of MART-1-specific T cells with rapamycin acted synergistically with IL-15, leading to significantly improved tumor-free survival in recipients with metastatic melanoma. These data demonstrate the practicality of using humanized mice to produce potentially unlimited source of tumor-specific human T cells for experimental and preclinical exploration of cancer immunotherapy. This study also suggests that pretreatment of tumor-reactive T cells with rapamycin in combination with IL-15 administration may be a novel strategy to improve the efficacy of adoptive T cell therapy.

DOI: 10.18632/oncotarget.7044
PubMed: 26824989
PubMed Central: PMC4872726

Affiliations:

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Le document en format XML

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<term>CD8-Positive T-Lymphocytes (immunology)</term>
<term>Cells, Cultured (MeSH)</term>
<term>Cytotoxicity, Immunologic (immunology)</term>
<term>HLA-A2 Antigen (immunology)</term>
<term>Humans (MeSH)</term>
<term>Immunization (MeSH)</term>
<term>Immunotherapy (MeSH)</term>
<term>Lymphocyte Activation (MeSH)</term>
<term>MART-1 Antigen (immunology)</term>
<term>Melanoma (immunology)</term>
<term>Melanoma (secondary)</term>
<term>Melanoma (therapy)</term>
<term>Mice (MeSH)</term>
<term>Mice, Inbred NOD (MeSH)</term>
<term>Mice, SCID (MeSH)</term>
<term>Peptide Fragments (administration & dosage)</term>
<term>Peptide Fragments (pharmacology)</term>
<term>T-Lymphocytes, Cytotoxic (immunology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Activation des lymphocytes (MeSH)</term>
<term>Animaux (MeSH)</term>
<term>Antigène HLA-A2 (immunologie)</term>
<term>Antigène MART-1 (immunologie)</term>
<term>Cellules cultivées (MeSH)</term>
<term>Cytotoxicité immunologique (immunologie)</term>
<term>Fragments peptidiques (administration et posologie)</term>
<term>Fragments peptidiques (pharmacologie)</term>
<term>Humains (MeSH)</term>
<term>Immunisation (MeSH)</term>
<term>Immunothérapie (MeSH)</term>
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<term>Lymphocytes T cytotoxiques (immunologie)</term>
<term>Mélanome (immunologie)</term>
<term>Mélanome (secondaire)</term>
<term>Mélanome (thérapie)</term>
<term>Souris (MeSH)</term>
<term>Souris SCID (MeSH)</term>
<term>Souris de lignée NOD (MeSH)</term>
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</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>HLA-A2 Antigen</term>
<term>MART-1 Antigen</term>
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<keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Fragments peptidiques</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigène HLA-A2</term>
<term>Antigène MART-1</term>
<term>Cytotoxicité immunologique</term>
<term>Lymphocytes T CD8+</term>
<term>Lymphocytes T cytotoxiques</term>
<term>Mélanome</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD8-Positive T-Lymphocytes</term>
<term>Cytotoxicity, Immunologic</term>
<term>Melanoma</term>
<term>T-Lymphocytes, Cytotoxic</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Fragments peptidiques</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Peptide Fragments</term>
</keywords>
<keywords scheme="MESH" qualifier="secondaire" xml:lang="fr"><term>Mélanome</term>
</keywords>
<keywords scheme="MESH" qualifier="secondary" xml:lang="en"><term>Melanoma</term>
</keywords>
<keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Melanoma</term>
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<term>Animaux</term>
<term>Cellules cultivées</term>
<term>Humains</term>
<term>Immunisation</term>
<term>Immunothérapie</term>
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<front><div type="abstract" xml:lang="en">A major factor hindering the exploration of adoptive immunotherapy in preclinical settings is the limited availability of tumor-reactive human T cells. Here we developed a humanized mouse model that permits large-scale production of human T cells expressing the engineered melanoma antigen MART-1-specific TCR. Humanized mice, made by transplantation of human fetal thymic tissue and CD34+ cells virally-transduced with HLA class I-restricted melanoma antigen (MART-1)-specific TCR gene, showed efficient development of MART-1-TCR+ human T cells with predominantly CD8+ cells. Importantly, MART-1-TCR+CD8+ T cells developing in these mice were capable of mounting antigen-specific responses in vivo, as evidenced by their proliferation, phenotypic conversion and IFN-γ production following MART-1 peptide immunization. Moreover, these MART-1-TCR+CD8+ T cells mediated efficient killing of melanoma cells in an HLA/antigen-dependent manner. Adoptive transfer of in vitro expanded MART-1-TCR+CD8+ T cells induced potent antitumor responses that were further enhanced by IL-15 treatment in melanoma-bearing recipients. Finally, a short incubation of MART-1-specific T cells with rapamycin acted synergistically with IL-15, leading to significantly improved tumor-free survival in recipients with metastatic melanoma. These data demonstrate the practicality of using humanized mice to produce potentially unlimited source of tumor-specific human T cells for experimental and preclinical exploration of cancer immunotherapy. This study also suggests that pretreatment of tumor-reactive T cells with rapamycin in combination with IL-15 administration may be a novel strategy to improve the efficacy of adoptive T cell therapy. </div>
</front>
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<ArticleTitle>Human melanoma immunotherapy using tumor antigen-specific T cells generated in humanized mice.</ArticleTitle>
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<Abstract><AbstractText>A major factor hindering the exploration of adoptive immunotherapy in preclinical settings is the limited availability of tumor-reactive human T cells. Here we developed a humanized mouse model that permits large-scale production of human T cells expressing the engineered melanoma antigen MART-1-specific TCR. Humanized mice, made by transplantation of human fetal thymic tissue and CD34+ cells virally-transduced with HLA class I-restricted melanoma antigen (MART-1)-specific TCR gene, showed efficient development of MART-1-TCR+ human T cells with predominantly CD8+ cells. Importantly, MART-1-TCR+CD8+ T cells developing in these mice were capable of mounting antigen-specific responses in vivo, as evidenced by their proliferation, phenotypic conversion and IFN-γ production following MART-1 peptide immunization. Moreover, these MART-1-TCR+CD8+ T cells mediated efficient killing of melanoma cells in an HLA/antigen-dependent manner. Adoptive transfer of in vitro expanded MART-1-TCR+CD8+ T cells induced potent antitumor responses that were further enhanced by IL-15 treatment in melanoma-bearing recipients. Finally, a short incubation of MART-1-specific T cells with rapamycin acted synergistically with IL-15, leading to significantly improved tumor-free survival in recipients with metastatic melanoma. These data demonstrate the practicality of using humanized mice to produce potentially unlimited source of tumor-specific human T cells for experimental and preclinical exploration of cancer immunotherapy. This study also suggests that pretreatment of tumor-reactive T cells with rapamycin in combination with IL-15 administration may be a novel strategy to improve the efficacy of adoptive T cell therapy. </AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Hu</LastName>
<ForeName>Zheng</ForeName>
<Initials>Z</Initials>
<AffiliationInfo><Affiliation>The First Bethune Hospital and Institute of Immunology, Jilin University, Changchun, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Xia</LastName>
<ForeName>Jinxing</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Fan</LastName>
<ForeName>Wei</ForeName>
<Initials>W</Initials>
<AffiliationInfo><Affiliation>The First Bethune Hospital and Institute of Immunology, Jilin University, Changchun, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wargo</LastName>
<ForeName>Jennifer</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yang</LastName>
<ForeName>Yong-Guang</ForeName>
<Initials>YG</Initials>
<AffiliationInfo><Affiliation>The First Bethune Hospital and Institute of Immunology, Jilin University, Changchun, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Columbia Center for Translational Immunology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.</Affiliation>
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Human melanoma immunotherapy using tumor antigen-specific T cells generated in humanized mice.

Human melanoma immunotherapy using tumor antigen-specific T cells generated in humanized mice.

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