{"id":1822,"date":"2021-05-16T14:31:00","date_gmt":"2021-05-16T18:31:00","guid":{"rendered":"https:\/\/nanobiotix.com\/resource\/radiation-therapy-enhanced-by-nbtxr3-nanoparticles-overcomes-anti-pd1-resistance-and-evokes-abscopal-effects\/"},"modified":"2024-10-29T08:50:16","modified_gmt":"2024-10-29T12:50:16","slug":"radiation-therapy-enhanced-by-nbtxr3-nanoparticles-overcomes-anti-pd1-resistance-and-evokes-abscopal-effects","status":"publish","type":"resource","link":"https:\/\/nanobiotix.com\/fr\/resource\/radiation-therapy-enhanced-by-nbtxr3-nanoparticles-overcomes-anti-pd1-resistance-and-evokes-abscopal-effects\/","title":{"rendered":"Radiation Therapy Enhanced by NBTXR3 Nanoparticles Overcomes Anti-PD1 Resistance and Evokes Abscopal Effects"},"content":{"rendered":"

[vc_row padding_top=”0″ padding_bottom=”0″ section_container_layout=”full-width” remove_horizontal_padding=”yes” module_type=”bg-color” gutter_size=”yes” equal_height=”yes” bg_color=”#28282e”][vc_column][vc_row_inner padding_top=”0″ padding_bottom=”0″ gutter_size=”yes” equal_height=”yes”][vc_column_inner column_paddings=”105″ column_position_vertical=”middle” column_min_height=”700″ column_min_height_sm=”400″ column_min_height_xs=”350″ module_type=”bg-image” bg_image=”102″ mask_fx=”yes-mask” mask_color_mode=”palette” mask_bg_color_palette=”main-mask” animation_fx=”yes-animation” animation_delay=”200″ animation_offset_scroll_down=”90″ width=”1\/2″ animation_in=”fadeInUp”][vc_empty_space height=”60px” responsive_lg=”hidden” responsive_md=”hidden”][az_box_icons box_icon_title=”Authors” box_icon_color_mode=”on-the-fly” icon_visibility=”yes-icon” icon_type=”font” icon=”fa fa-edit” icon_color_mode=”on-the-fly” icon_size=”50″ box_icon_color=”#ffffff” icon_color=”#ffffff”]Yun Hu PhD1<\/span>, S\u00e9bastien Paris PhD2<\/span>, Hampartsoum Barsoumian PhD1<\/span>, Chike O. Abana MD, PhD1<\/span>, Kewen He MD3<\/span>, Mark Wasley BS1<\/span>, Ahmed I. Younes MD4<\/span>, Fatemeh Masrorpour MS1<\/span>, Dawei Chen MD, PhD5<\/span>, Liangpeng Yang PhD1<\/span>, Joe Dan Dunn PhD1<\/span>, Jie Zhang MD1, Saumil Gandhi MD, PhD1<\/span>, Quynh-Nhu Nguyen MD1<\/span>, Maria Angelica Cortez PhD1<\/span>, James Welsh MD6<\/span> 1 – Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas 2 – Department of Translational Science, Nanobiotix, Paris, France 3 – Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China 4 – East Carolina University, Greenville, North Carolina 5 – Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China 6 – Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas. Electronic address: jwelsh@mdanderson.org <\/span>[\/az_box_icons][vc_empty_space height=”60px” responsive_lg=”hidden” responsive_md=”hidden”][\/vc_column_inner][vc_column_inner column_paddings=”105″ column_position_vertical=”middle” module_type=”bg-color” animation_fx=”yes-animation” animation_delay=”300″ animation_offset_scroll_down=”90″ width=”1\/2″ bg_color=”#ffffff” animation_in=”fadeInUp”][vc_empty_space height=”60px” responsive_lg=”hidden” responsive_md=”hidden”][az_box_icons box_icon_title=”Summary” icon_visibility=”yes-icon” icon_type=”font” icon=”az-icon az-icon-layers2″ icon_color_mode=”on-the-fly” icon_color=”#28282e” icon_size=”50″]Purpose:<\/strong> Radiation combined with PD1 blockade offers significant treatment benefits in several tumor types; however, anti-PD1 resistance precludes such benefits in many cases. Here we attempted to overcome anti-PD1 resistance by combining localized radiation with a radioenhancing nanoparticle (NBTXR3) and systemic anti-PD1 treatment to achieve abscopal effects in an anti-PD1-resistant mouse model of lung cancer. Methods and Materials:<\/strong> Female 129Sv\/Ev mice were inoculated with 344SQ anti-PD1-resistant (344SQR) or anti-PD1-sensitive (344SQP) metastatic lung cancer cells in the right leg on day 0 (\u201cprimary\u201d tumor) and the left leg on day 4 (\u201csecondary\u201d tumor). Primary tumors were injected intratumorally with NBTXR3 on day 7 and were irradiated with 12 Gy on days 8, 9, and 10. Mice were given 6 intraperitoneal injections of anti-PD1. T cell receptor repertoire was analyzed in tumor samples with RNA sequencing, infiltration of CD8 T cells with immunohistochemical staining, and activities of various immune pathways with NanoString analysis. Results:<\/strong> The triple combination of NBTXR3 with localized radiation and systemic anti-PD1 significantly delayed the growth of both irradiated and unirradiated tumors in both 344SQP and 344SQR tumor models. NBTXR3 remodeled the immune microenvironment of unirradiated tumors by triggering the activation of various immune pathways, increasing the number of CD8+ T cells, and modifying the T cell receptor repertoire in the 344SQR tumor model. Conclusions:<\/strong> The ability of NBTXR3 to evoke significant abscopal effects in both anti-PD1-sensitive and anti-PD1-resistant lung cancers could open the possibility of its use for treating patients with metastatic lung cancer regardless of sensitivity (or resistance) to immunotherapies.[\/az_box_icons][vc_empty_space height=”60px” responsive_lg=”hidden” responsive_md=”hidden”][\/vc_column_inner][\/vc_row_inner][\/vc_column][\/vc_row]<\/p>\n","protected":false},"featured_media":0,"menu_order":0,"template":"","meta":{"_acf_changed":false,"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"wds_primary_resource_type":0,"wds_primary_data_type":0,"wds_primary_indication":0,"wds_primary_platform_type":0,"footnotes":""},"resource_type":[23,24],"data_type":[29],"indication":[],"platform_type":[36],"class_list":["post-1822","resource","type-resource","status-publish","hentry","resource_type-no-rights","resource_type-publications","data_type-pre-clinical","platform_type-nbtxr3"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/resource\/1822","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/resource"}],"about":[{"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/types\/resource"}],"version-history":[{"count":0,"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/resource\/1822\/revisions"}],"wp:attachment":[{"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/media?parent=1822"}],"wp:term":[{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/resource_type?post=1822"},{"taxonomy":"data_type","embeddable":true,"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/data_type?post=1822"},{"taxonomy":"indication","embeddable":true,"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/indication?post=1822"},{"taxonomy":"platform_type","embeddable":true,"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/platform_type?post=1822"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}