Frontiers in Immunology.
2024-10;
Xinhui Hui1†Muhammad Asad Farooq,&#x;Muhammad Asad Farooq1,2†Yiran ChenYiran Chen1Iqra Ajmal,Iqra Ajmal1,2Yaojun Ren,Yaojun Ren1,3Min XueMin Xue1Yuzhou JiYuzhou Ji1Bingtan DuBingtan Du1Shijia WuShijia Wu1Wenzheng Jiang*&#x;Wenzheng Jiang1*‡</span>
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<td class="td-service-name"><span class='bt-span'><a title='Nucleic Acid Purification & Analysis' target=_blank href='/Molecular_Biology_Products.html?src=ReferenceNew2'>Nucleic Acid Purification & Analysis</></a></span></td>
<td rowspan="1" class="td-detail"> Primary T cells were positively selected with CD4 and CD8 microbeads, stimulated with Enceed™ (<strong>Genscript</strong>, Nanjing, China) for 48 hours, and subsequently cultured in X-VIVO 15 </td>
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<p>Background: Solid tumors are characterized by a low blood supply, complex stromal architecture, and immunosuppressive milieu, which inhibit CAR-T cell entry and survival. CXCR5 has previously been employed to increase CAR-T cell infiltration into CXCL13+ cancers. On the other hand, IL-7 improves the survival and persistence of T cells inside a solid tumor milieu.
Methods: We constructed a novel NKG2D-based CAR (C5/IL7-CAR) that co-expressed CXCR5 and IL-7. The human osteosarcoma cell lines U-2 OS, 143B, and Mg63 highly expressed MICA/B and CXCL13, thus presenting a perfect avenue for the present study.
Results: Novel CAR-T cells are superior in their activation, degranulation, and cytokine release compete... <span style="cursor: pointer;color:#046CA6"
onclick="more('#moreinfo')">More</span></p>
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style="display: none;">Background: Solid tumors are characterized by a low blood supply, complex stromal architecture, and immunosuppressive milieu, which inhibit CAR-T cell entry and survival. CXCR5 has previously been employed to increase CAR-T cell infiltration into CXCL13+ cancers. On the other hand, IL-7 improves the survival and persistence of T cells inside a solid tumor milieu.
Methods: We constructed a novel NKG2D-based CAR (C5/IL7-CAR) that co-expressed CXCR5 and IL-7. The human osteosarcoma cell lines U-2 OS, 143B, and Mg63 highly expressed MICA/B and CXCL13, thus presenting a perfect avenue for the present study.
Results: Novel CAR-T cells are superior in their activation, degranulation, and cytokine release competence, hence lysing more target cells than conventional CAR. Furthermore, CXCR5 and IL-7 co-expression decreased the expression of PD-1, TIM-3, and TIGIT and increased Bcl-2 expression. Novel CAR-T cells show enhanced proliferation and differentiation towards the stem cell memory T cell phenotype. C5/IL7-CAR-T cells outperformed conventional CAR-T in eradicating osteosarcoma in mouse models and displayed better survival. Additionally, CXCR5 and IL-7 co-expression enhanced CAR-T cell numbers, cytokine release, and survival in implanted tumor tissues compared to conventional CAR-T cells. Mechanistically, C5/IL7-CAR-T cells displayed enhanced STAT5 signaling.
Conclusion: These findings highlight the potential of CXCR5 and IL-7 co-expression to improve CAR-T cell therapy efficacy against osteosarcoma.</div>
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<a href="https://doi.org/doi.org/10.3389/fimmu.2024.1462076" target="_blank" rel="external nofollow">Article Link ></a>
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cursor: pointer;
background: #1D73DD !important;
border: 1px solid #1D73DD !important;
color: #fff !important;
}
.ui-dialog-buttonset button {
padding: 4px 10px !important;
border-radius: 2px !important;
outline: none !important;
color: #1d73dd!important;
}
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padding: 4px 10px !important;
border: 1px solid #004B95 !important;
border-radius: 2px !important;
background: #004B95 !important;
color: #fff !important;
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color: #fff !important;
}
.ui-dialog-buttonset button:nth-child(2) {
padding: 4px 10px !important;
border-radius: 2px !important;
outline: none !important;
background-color: #fff !important;
border: 1px solid #1D73DD !important;
color: #1D73DD !important;
}
.ui-dialog-buttonset button:nth-child(2):hover {
padding: 4px 10px !important;
border-radius: 2px !important;
background-color: #f6f9ff !important;
border: 1px solid #004B95 !important;
color: #004B95 !important;
}
.ui-dialog-buttonset button:nth-child(2):hover .ui-button-text{
color: #1D73DD !important;
}
</style>
<script>
function show_alert_dialog(info,title,link){
if(!title){
title = "提示";
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$('#show_alert').html(info);
$('#show_alert').dialog({
width:520,
modal:true,
title:title,
buttons: {
关闭: function() {
if(link){
window.location = link;
$( this ).dialog( "close" );
}else{
$( this ).dialog( "close" );
}
}
},
});
}
</script>
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