{"id":21245,"date":"2025-05-16T05:50:25","date_gmt":"2025-05-16T05:50:25","guid":{"rendered":"https:\/\/www.ttci-th.org\/?p=21245"},"modified":"2025-08-19T09:53:56","modified_gmt":"2025-08-19T09:53:56","slug":"pdl1-gemcitabine-lung-cancer","status":"publish","type":"post","link":"https:\/\/www.ttci-th.org\/th\/pdl1-gemcitabine-lung-cancer\/","title":{"rendered":"Enhancing T cell cytotoxicity against lung cancer with an \u03b1PD-L1 protein engager and gemcitabine combination therapy"},"content":{"rendered":"<div data-elementor-type=\"wp-post\" data-elementor-id=\"21245\" class=\"elementor elementor-21245\">\n\t\t\t\t\t\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-32163b7 elementor-section-boxed elementor-section-height-default elementor-section-height-default wpr-particle-no wpr-jarallax-no wpr-parallax-no\" data-id=\"32163b7\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-9247286\" data-id=\"9247286\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t\t\t<div class=\"elementor-element elementor-element-31ef166 elementor-widget elementor-widget-text-editor\" data-id=\"31ef166\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.16.0 - 14-09-2023 *\/\n.elementor-widget-text-editor.elementor-drop-cap-view-stacked .elementor-drop-cap{background-color:#69727d;color:#fff}.elementor-widget-text-editor.elementor-drop-cap-view-framed .elementor-drop-cap{color:#69727d;border:3px solid;background-color:transparent}.elementor-widget-text-editor:not(.elementor-drop-cap-view-default) .elementor-drop-cap{margin-top:8px}.elementor-widget-text-editor:not(.elementor-drop-cap-view-default) .elementor-drop-cap-letter{width:1em;height:1em}.elementor-widget-text-editor .elementor-drop-cap{float:left;text-align:center;line-height:1;font-size:50px}.elementor-widget-text-editor .elementor-drop-cap-letter{display:inline-block}<\/style>\t\t\t\t<p>\u2022 Researchers have developed a new drug called \u03b1PD-L1 \u00d7 \u03b1CD3 BIPE that helps the immune system better target and kill non-small cell lung cancer cells by connecting cancer-fighting T cells directly to cancer cells expressing high levels of PD-L1, a protein that usually helps tumors evade immunity. Laboratory tests showed that this drug significantly improved T cell\u2013mediated cancer cell destruction, especially when combined with the chemotherapy drug gemcitabine, which boosts the cancer cells\u2019 visibility to the immune system. This combined approach shows promise as a more effective treatment for lung cancer by enhancing the body\u2019s natural immune response.<\/p><p>\u2022 The overexpression of programmed cell death ligand 1 (PD-L1), a critical immune checkpoint protein, is associated with poor prognosis and reduced survival in lung cancer patients. Monoclonal antibodies targeting the PD-1\/PD-L1 axis have been approved to disrupt this interaction and prevent immune cell exhaustion. Herein, to enhance the efficacy of PD-1\/PD-L1 blockade, we investigated a bispecific \u03b1PD-L1 \u00d7\u03b1CD3 protein engager (\u03b1PD-L1 \u00d7\u03b1CD3 BIPE). The \u03b1PD-L1 \u00d7\u03b1CD3 BIPE consists of an anti-CD3 single-chain variable fragment (scFv) linked to an anti-PD-L1 scFv, allowing it to bind to CD3-positive T cells simultaneously and PD-L1-overexpressing cancer cells. In co-culture assays with T cells and non-small cell lung cancer (NSCLC) cell lines-A549, NCI-H460, and NCI-H1975-treatment with the BIPE significantly enhanced T-cell-mediated cytotoxicity. The killing efficiency correlated with PD-L1 expression levels, with the highest cytotoxic activity observed in NCI-H1975 (high PD-L1 expression), followed by NCI-H460 (moderate PD-L1 expression) and A549 (low PD-L1 expression). Furthermore, combining the BIPE with the standard chemotherapeutic agent gemcitabine further improved anti-tumor activity. This effect was likely due to gemcitabine-induced upregulation of PD-L1 and MHC class I expression on cancer cells, enhancing T-cell recognition and cytotoxicity. These findings suggest that combining \u03b1PD-L1 \u00d7\u03b1CD3 BIPE with gemcitabine is promising for enhancing immune checkpoint blockade and augmenting anti-tumor immunity in NSCLC.<\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-6e75882 elementor-section-boxed elementor-section-height-default elementor-section-height-default wpr-particle-no wpr-jarallax-no wpr-parallax-no\" data-id=\"6e75882\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-16220c7\" data-id=\"16220c7\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t\t\t<div class=\"elementor-element elementor-element-0386e6f elementor-widget elementor-widget-spacer\" data-id=\"0386e6f\" data-element_type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.16.0 - 14-09-2023 *\/\n.elementor-column .elementor-spacer-inner{height:var(--spacer-size)}.e-con{--container-widget-width:100%}.e-con-inner>.elementor-widget-spacer,.e-con>.elementor-widget-spacer{width:var(--container-widget-width,var(--spacer-size));--align-self:var(--container-widget-align-self,initial);--flex-shrink:0}.e-con-inner>.elementor-widget-spacer>.elementor-widget-container,.e-con>.elementor-widget-spacer>.elementor-widget-container{height:100%;width:100%}.e-con-inner>.elementor-widget-spacer>.elementor-widget-container>.elementor-spacer,.e-con>.elementor-widget-spacer>.elementor-widget-container>.elementor-spacer{height:100%}.e-con-inner>.elementor-widget-spacer>.elementor-widget-container>.elementor-spacer>.elementor-spacer-inner,.e-con>.elementor-widget-spacer>.elementor-widget-container>.elementor-spacer>.elementor-spacer-inner{height:var(--container-widget-height,var(--spacer-size))}.e-con-inner>.elementor-widget-spacer.elementor-widget-empty,.e-con>.elementor-widget-spacer.elementor-widget-empty{position:relative;min-height:22px;min-width:22px}.e-con-inner>.elementor-widget-spacer.elementor-widget-empty .elementor-widget-empty-icon,.e-con>.elementor-widget-spacer.elementor-widget-empty .elementor-widget-empty-icon{position:absolute;top:0;bottom:0;left:0;right:0;margin:auto;padding:0;width:22px;height:22px}<\/style>\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-cb58e40 elementor-section-boxed elementor-section-height-default elementor-section-height-default wpr-particle-no wpr-jarallax-no wpr-parallax-no\" data-id=\"cb58e40\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-22372e9\" data-id=\"22372e9\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t\t\t<div class=\"elementor-element elementor-element-d30471e elementor-widget__width-initial elementor-widget elementor-widget-heading\" data-id=\"d30471e\" data-element_type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.16.0 - 14-09-2023 *\/\n.elementor-heading-title{padding:0;margin:0;line-height:1}.elementor-widget-heading .elementor-heading-title[class*=elementor-size-]>a{color:inherit;font-size:inherit;line-height:inherit}.elementor-widget-heading .elementor-heading-title.elementor-size-small{font-size:15px}.elementor-widget-heading .elementor-heading-title.elementor-size-medium{font-size:19px}.elementor-widget-heading .elementor-heading-title.elementor-size-large{font-size:29px}.elementor-widget-heading .elementor-heading-title.elementor-size-xl{font-size:39px}.elementor-widget-heading .elementor-heading-title.elementor-size-xxl{font-size:59px}<\/style><h2 class=\"elementor-heading-title elementor-size-default\">\u0e40\u0e07\u0e34\u0e19\u0e17\u0e38\u0e19<\/h2>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-6aeec7e elementor-widget-divider--view-line elementor-widget elementor-widget-divider\" data-id=\"6aeec7e\" data-element_type=\"widget\" data-widget_type=\"divider.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.16.0 - 14-09-2023 *\/\n.elementor-widget-divider{--divider-border-style:none;--divider-border-width:1px;--divider-color:#0c0d0e;--divider-icon-size:20px;--divider-element-spacing:10px;--divider-pattern-height:24px;--divider-pattern-size:20px;--divider-pattern-url:none;--divider-pattern-repeat:repeat-x}.elementor-widget-divider .elementor-divider{display:flex}.elementor-widget-divider .elementor-divider__text{font-size:15px;line-height:1;max-width:95%}.elementor-widget-divider .elementor-divider__element{margin:0 var(--divider-element-spacing);flex-shrink:0}.elementor-widget-divider .elementor-icon{font-size:var(--divider-icon-size)}.elementor-widget-divider .elementor-divider-separator{display:flex;margin:0;direction:ltr}.elementor-widget-divider--view-line_icon .elementor-divider-separator,.elementor-widget-divider--view-line_text .elementor-divider-separator{align-items:center}.elementor-widget-divider--view-line_icon .elementor-divider-separator:after,.elementor-widget-divider--view-line_icon .elementor-divider-separator:before,.elementor-widget-divider--view-line_text .elementor-divider-separator:after,.elementor-widget-divider--view-line_text .elementor-divider-separator:before{display:block;content:\"\";border-bottom:0;flex-grow:1;border-top:var(--divider-border-width) var(--divider-border-style) var(--divider-color)}.elementor-widget-divider--element-align-left .elementor-divider .elementor-divider-separator>.elementor-divider__svg:first-of-type{flex-grow:0;flex-shrink:100}.elementor-widget-divider--element-align-left .elementor-divider-separator:before{content:none}.elementor-widget-divider--element-align-left .elementor-divider__element{margin-left:0}.elementor-widget-divider--element-align-right .elementor-divider .elementor-divider-separator>.elementor-divider__svg:last-of-type{flex-grow:0;flex-shrink:100}.elementor-widget-divider--element-align-right .elementor-divider-separator:after{content:none}.elementor-widget-divider--element-align-right .elementor-divider__element{margin-right:0}.elementor-widget-divider:not(.elementor-widget-divider--view-line_text):not(.elementor-widget-divider--view-line_icon) .elementor-divider-separator{border-top:var(--divider-border-width) var(--divider-border-style) var(--divider-color)}.elementor-widget-divider--separator-type-pattern{--divider-border-style:none}.elementor-widget-divider--separator-type-pattern.elementor-widget-divider--view-line .elementor-divider-separator,.elementor-widget-divider--separator-type-pattern:not(.elementor-widget-divider--view-line) .elementor-divider-separator:after,.elementor-widget-divider--separator-type-pattern:not(.elementor-widget-divider--view-line) .elementor-divider-separator:before,.elementor-widget-divider--separator-type-pattern:not([class*=elementor-widget-divider--view]) .elementor-divider-separator{width:100%;min-height:var(--divider-pattern-height);-webkit-mask-size:var(--divider-pattern-size) 100%;mask-size:var(--divider-pattern-size) 100%;-webkit-mask-repeat:var(--divider-pattern-repeat);mask-repeat:var(--divider-pattern-repeat);background-color:var(--divider-color);-webkit-mask-image:var(--divider-pattern-url);mask-image:var(--divider-pattern-url)}.elementor-widget-divider--no-spacing{--divider-pattern-size:auto}.elementor-widget-divider--bg-round{--divider-pattern-repeat:round}.rtl .elementor-widget-divider .elementor-divider__text{direction:rtl}.e-con-inner>.elementor-widget-divider,.e-con>.elementor-widget-divider{width:var(--container-widget-width,100%);--flex-grow:var(--container-widget-flex-grow)}<\/style>\t\t<div class=\"elementor-divider\">\n\t\t\t<span class=\"elementor-divider-separator\">\n\t\t\t\t\t\t<\/span>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-86b218e elementor-widget elementor-widget-text-editor\" data-id=\"86b218e\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p>This research project was supported by Fundamental Fund 2024,<br \/>Chiang Mai University (Grant ID FF039\/2567), Siriraj Research Funds<br \/>(R016737004) from the Faculty of Medicine Siriraj Hospital, Mahidol<br \/>University, and the School of Medical Sciences, University of Phayao<br \/>(Grants No. MS 251001).<\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-513a232 elementor-section-boxed elementor-section-height-default elementor-section-height-default wpr-particle-no wpr-jarallax-no wpr-parallax-no\" data-id=\"513a232\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-7709a77\" data-id=\"7709a77\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t\t\t<div class=\"elementor-element elementor-element-1fc1ca7 elementor-widget elementor-widget-spacer\" data-id=\"1fc1ca7\" data-element_type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-f5f587e elementor-section-boxed elementor-section-height-default elementor-section-height-default wpr-particle-no wpr-jarallax-no wpr-parallax-no\" data-id=\"f5f587e\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-03bcea0\" data-id=\"03bcea0\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t\t\t<div class=\"elementor-element elementor-element-ca5ef47 elementor-widget__width-initial elementor-widget elementor-widget-heading\" data-id=\"ca5ef47\" data-element_type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">\n\u0e01\u0e23\u0e30\u0e14\u0e32\u0e29\u0e15\u0e49\u0e19\u0e09\u0e1a\u0e31\u0e1a<\/h2>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-2a9807c elementor-widget-divider--view-line elementor-widget elementor-widget-divider\" data-id=\"2a9807c\" data-element_type=\"widget\" data-widget_type=\"divider.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<div class=\"elementor-divider\">\n\t\t\t<span class=\"elementor-divider-separator\">\n\t\t\t\t\t\t<\/span>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-89bfba8 elementor-widget__width-initial elementor-widget elementor-widget-text-editor\" data-id=\"89bfba8\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<p><strong>\u0e0a\u0e37\u0e48\u0e2d\u0e1a\u0e17\u0e04\u0e27\u0e32\u0e21\u0e15\u0e49\u0e19\u0e09\u0e1a\u0e31\u0e1a:<\/strong> Enhancing T cell cytotoxicity against lung cancer with an \u03b1PD-L1 protein engager and gemcitabine combination therapy<br \/><strong>\u0e27\u0e32\u0e23\u0e2a\u0e32\u0e23:<\/strong> Biomedicine &amp; Pharmacotherapy<br \/><strong>\u0e14\u0e2d\u0e22: <\/strong><a href=\"https:\/\/doi.org\/10.1016\/j.biopha.2025.118161\">https:\/\/doi.org\/10.1016\/j.biopha.2025.118161<\/a><\/p>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-2cc934e elementor-section-boxed elementor-section-height-default elementor-section-height-default wpr-particle-no wpr-jarallax-no wpr-parallax-no\" data-id=\"2cc934e\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-9bf8d38\" data-id=\"9bf8d38\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t\t\t<div class=\"elementor-element elementor-element-4b1861f elementor-widget elementor-widget-spacer\" data-id=\"4b1861f\" data-element_type=\"widget\" data-widget_type=\"spacer.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<div class=\"elementor-spacer\">\n\t\t\t<div class=\"elementor-spacer-inner\"><\/div>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-5c5d082 elementor-section-boxed elementor-section-height-default elementor-section-height-default wpr-particle-no wpr-jarallax-no wpr-parallax-no\" data-id=\"5c5d082\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-d7e3d8d\" data-id=\"d7e3d8d\" data-element_type=\"column\">\n\t\t\t<div class=\"elementor-widget-wrap elementor-element-populated\">\n\t\t\t\t\t\t\t\t<div class=\"elementor-element elementor-element-8a45000 elementor-widget__width-initial elementor-widget elementor-widget-heading\" data-id=\"8a45000\" data-element_type=\"widget\" data-widget_type=\"heading.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<h2 class=\"elementor-heading-title elementor-size-default\">\u0e08\u0e14\u0e2b\u0e21\u0e32\u0e22\u0e42\u0e15\u0e49\u0e15\u0e2d\u0e1a<\/h2>\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-6aa3269 elementor-widget-divider--view-line elementor-widget elementor-widget-divider\" data-id=\"6aa3269\" data-element_type=\"widget\" data-widget_type=\"divider.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t<div class=\"elementor-divider\">\n\t\t\t<span class=\"elementor-divider-separator\">\n\t\t\t\t\t\t<\/span>\n\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<div class=\"elementor-element elementor-element-8df055a elementor-widget__width-initial elementor-widget elementor-widget-text-editor\" data-id=\"8df055a\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t\t\t\t\t<ul><li>Aussara Panya (<a href=\"mailto:aussara.pan@cmu.ac.th\">aussara.pan@cmu.ac.th<\/a>)<\/li><\/ul>\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t\t\t\t\t\t\t<\/div>\n\t\t<\/section>\n\t\t\t\t<section class=\"elementor-section elementor-top-section elementor-element elementor-element-a2a0cb4 elementor-section-boxed elementor-section-height-default elementor-section-height-default wpr-particle-no wpr-jarallax-no wpr-parallax-no\" data-id=\"a2a0cb4\" data-element_type=\"section\">\n\t\t\t\t\t\t<div class=\"elementor-container elementor-column-gap-default\">\n\t\t\t\t\t<div class=\"elementor-column elementor-col-100 elementor-top-column elementor-element elementor-element-8067b9b\" data-id=\"8067b9b\" data-element_type=\"column\">\n\t\t\t<div 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