Journal of translational research最新文献

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Murine models for triple-negative breast cancer with differential responsiveness to immunotherapy. 对免疫治疗具有不同反应性的三阴性乳腺癌小鼠模型。

Journal of translational research Pub Date : 2026-01-01 Epub Date: 2026-05-05 DOI: 10.1080/29947448.2026.2664260

Thomas J Kalantzakos, Yufan Zhou, Xingyu Liu, Joshua Proehl, Cameron Durfee, Ian Tamayo, Nuri Alpay Temiz, Benjamin Troness, Anusha Soni, Harshita B Gupta, Reuben S Harris

{"title":"Murine models for triple-negative breast cancer with differential responsiveness to immunotherapy.","authors":"Thomas J Kalantzakos, Yufan Zhou, Xingyu Liu, Joshua Proehl, Cameron Durfee, Ian Tamayo, Nuri Alpay Temiz, Benjamin Troness, Anusha Soni, Harshita B Gupta, Reuben S Harris","doi":"10.1080/29947448.2026.2664260","DOIUrl":"10.1080/29947448.2026.2664260","url":null,"abstract":"Breast cancer is the most common cancer diagnosis in women. Clinical studies with triple-negative breast cancer (TNBC) are encouraging for immunotherapy combined with chemotherapy (anti-PD-1 with paclitaxel and/or carboplatin). However, additional clinical advances may be pursued more rapidly with assistance from preclinical TNBC models including syngeneic mammary tumor cell lines. Here, we report two mammary tumor cell lines that exhibit differential responsiveness to immunotherapy in vivo. Spontaneous mammary tumors from C57BL/6J MMTV-Cre Trp53fl/+ animals were passaged serially in cell culture and in vivo in the mammary fat pad of fully wildtype animals. The resulting lines, MM001i and MM008i, lost Trp53 and formed 1000 mm3 tumors in the mammary fat pad within 21-28 days. Despite originating from the same genetic background, these lines exhibit differential responses to immunotherapy. For anti-PD-1 therapy, MM001i is poorly responsive and MM008i is strongly responsive with near-complete tumor regression. In comparison, both MM001i and MM008i respond rapidly to anti-CTLA-4 therapy. Both models express unique tumor antigens as evidenced by immunity to subsequent engraftments. Primary MM008i tumors exhibit greater T cell infiltration, and CD8-positive T lymphocytes are required for anti-PD-1 responses. These TNBC models are promising for further mechanistic studies and testing future single and combinatorial therapies.","PeriodicalId":524227,"journal":{"name":"Journal of translational research","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149077443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CRISPR/Cas9 gene editing in hematopoietic stem and progenitor cells to accelerate the translation of cellular therapies and immunotherapies. CRISPR/Cas9基因编辑造血干细胞和祖细胞，加速细胞疗法和免疫疗法的转化。

Journal of translational research Pub Date : 2026-01-01 Epub Date: 2026-06-02 DOI: 10.1080/29947448.2026.2660423

Laura Falceto Font, Dan Jin, John Figg, Connor Francis, Kaytora Long-James, Jeffrey Drake, Alexandra Reid, Caitland Love, Brianna McDonald, David Hilferty, Hector Mendez-Gomez, Rachael Bessey, Fernanda Pohl-Guimarães, Duane Mitchell, Zubaidan Tuerdi, Evelyne Lauret, Catherine Flores

{"title":"CRISPR/Cas9 gene editing in hematopoietic stem and progenitor cells to accelerate the translation of cellular therapies and immunotherapies.","authors":"Laura Falceto Font, Dan Jin, John Figg, Connor Francis, Kaytora Long-James, Jeffrey Drake, Alexandra Reid, Caitland Love, Brianna McDonald, David Hilferty, Hector Mendez-Gomez, Rachael Bessey, Fernanda Pohl-Guimarães, Duane Mitchell, Zubaidan Tuerdi, Evelyne Lauret, Catherine Flores","doi":"10.1080/29947448.2026.2660423","DOIUrl":"10.1080/29947448.2026.2660423","url":null,"abstract":"Hematopoietic stem and progenitor cells (HSPCs) play a critical role in immune system regeneration and have therapeutic potential in hematological disorders and immunotherapy. However, gene editing in HSPCs remains challenging, particularly in murine HSPCs, limiting preclinical studies and translational advancements. Here, we present a CRISPR/Cas9 mRNA-based protocol for efficient gene editing of human CD34+ HSPCs and murine HSPCs. Using electroporation of Cas9 mRNA and sgRNAs, we achieved up to 80% gene knock-down in HSPCs while retaining cell viability. Edited murine HSPCs successfully reconstituted bone marrow in lethally irradiated mice, demonstrating functional engraftment. We also demonstrated that knocking-out IL-6R in murine HSPCs and CD34+ cells skewed myeloid differentiation toward less immunosuppressive phenotypes, and combining IL-6R-knock-out murine HSPCs with immune checkpoint inhibitors enhanced glioma treatment efficacy in preclinical models, showcasing the potential of this method to facilitate translation of cellular therapies. This method offers a scalable and cost-effective approach to genetic modification of HSPCs, supporting advancements in hematopoietic stem cell transplants (HSCTs) and next-generation immunotherapies. By streamlining gene editing for both preclinical and translational applications, this protocol has the potential to accelerate the development of personalised cellular therapies and improve clinical outcomes in oncology and immune-related disorders.","PeriodicalId":524227,"journal":{"name":"Journal of translational research","volume":"3 1","pages":"2660423"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13616094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0