Combination IFNβ and Membrane-Stable CD40L Maximize Tumor Dendritic Cell Activation and Lymph Node Trafficking to Elicit Systemic T-cell Immunity
| العنوان: | Combination IFNβ and Membrane-Stable CD40L Maximize Tumor Dendritic Cell Activation and Lymph Node Trafficking to Elicit Systemic T-cell Immunity |
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| المؤلفون: | Hong Zheng, Xiaoqing Yu, Mohammed L. Ibrahim, Dana Foresman, Mengyu Xie, Joseph O. Johnson, Theresa A. Boyle, Brian Ruffell, Bradford A. Perez, Scott J. Antonia, Neal Ready, Andreas N. Saltos, Mark J. Cantwell, Amer A. Beg |
| المصدر: | Cancer Immunology Research. 11:466-485 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Cancer Research, Immunology |
| الوصف: | Oncolytic virus therapies induce the direct killing of tumor cells and activation of conventional dendritic cells (cDC); however, cDC activation has not been optimized with current therapies. We evaluated the adenoviral delivery of engineered membrane-stable CD40L (MEM40) and IFNβ to locally activate cDCs in mouse tumor models. Combined tumor MEM40 and IFNβ expression induced the highest cDC activation coupled with increased lymph node migration, increased systemic antitumor CD8+ T-cell responses, and regression of established tumors in a cDC1-dependent manner. MEM40 + IFNβ combined with checkpoint inhibitors led to effective control of distant tumors and lung metastases. An oncolytic adenovirus (MEM-288) expressing MEM40 + IFNβ in phase I clinical testing induced cancer cell loss concomitant with enhanced T-cell infiltration and increased systemic presence of tumor T-cell clonotypes in non–small cell lung cancer (NSCLC) patients. This approach to simultaneously target two major DC-activating pathways has the potential to significantly affect the solid tumor immunotherapy landscape. |
| تدمد: | 2326-6074 2326-6066 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::eac691aa91b18f80c6b6947b60ebee43Test https://doi.org/10.1158/2326-6066.cir-22-0927Test |
| رقم الانضمام: | edsair.doi...........eac691aa91b18f80c6b6947b60ebee43 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23266074 23266066 |
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