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CAR T-cell therapy for pancreatic cancer. ​

文献信息 ​

DOI10.1002/jso.24627
PMID28346697
期刊Journal of surgical oncology
影响因子1.9
JCR 分区Q2
发表年份2017
被引次数51
关键词CAR T细胞, 过继细胞治疗, 免疫检查点抑制, 嵌合抗原受体, 免疫治疗
文献类型Journal Article, Review
ISSN0022-4790
页码63-74
期号116(1)
作者Carl J DeSelm, Zachary E Tano, Anna M Varghese, Prasad S Adusumilli

一句话小结 ​

本研究探讨了嵌合抗原受体（CAR）T细胞疗法在靶向胰腺癌中的应用，指出尽管该疗法在血液恶性肿瘤中表现出显著疗效，但其在实体瘤中的实施面临肿瘤微环境和免疫检查点表达等多重挑战。研究为未来优化CAR T细胞疗法提供了重要的理论基础和实践方向。

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CAR T细胞 · 过继细胞治疗 · 免疫检查点抑制 · 嵌合抗原受体 · 免疫治疗

摘要 ​

嵌合抗原受体（CAR）T细胞疗法利用基因工程技术重新定向患者自身的T细胞，以靶向癌细胞。在血液恶性肿瘤中的显著疗效促使人们探索这一方法在胰腺癌等实体瘤中的应用。然而，复杂的肿瘤微环境、基质对免疫反应的限制以及T细胞上免疫检查点的表达都带来了挑战。在此，我们总结了使用CAR T细胞疗法靶向胰腺癌的机遇、挑战以及当前的知识状态。

英文摘要 ​

Chimeric antigen receptor (CAR) T-cell therapy utilizes genetic engineering to redirect a patient's own T cells to target cancer cells. The remarkable results in hematological malignancies prompted investigating this approach in solid tumors such as pancreatic cancer. The complex tumor microenvironment, stromal hindrance in limiting immune response, and expression of checkpoint blockade on T cells pose hurdles. Herein, we summarize the opportunities, challenges, and state of knowledge in targeting pancreatic cancer with CAR T-cell therapy.

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主要研究问题 ​

  1. 除了胰腺癌，CAR T细胞疗法在其他实体瘤中的应用现状如何？
  2. 在胰腺癌的治疗中，CAR T细胞疗法面临哪些具体的免疫微环境挑战？
  3. 目前有哪些方法可以克服CAR T细胞疗法在胰腺癌中的疗效限制？
  4. CAR T细胞疗法与传统治疗（如化疗、放疗）在胰腺癌治疗中的比较研究有哪些？
  5. 针对胰腺癌的CAR T细胞疗法正在进行哪些临床试验，结果如何？

核心洞察 ​

研究背景和目的 ​

胰腺导管腺癌（PDAC）是美国最常见的胰腺癌类型，预计到2030年将成为第二大癌症死亡原因。尽管在化疗方面取得了一些进展，但该疾病的中位生存期仍然较短（<1年），急需新治疗策略。本文综述了CAR T细胞治疗在胰腺癌中的应用现状、面临的挑战及未来的研究方向。

主要方法/材料/实验设计 ​

CAR T细胞治疗通过基因工程技术，重定向患者自身的T细胞以靶向癌细胞。针对胰腺癌的CAR T细胞治疗的主要研究方法包括：

  1. 抗原选择：选择在胰腺癌细胞中高表达而在正常细胞中低表达的抗原，如间皮素（MSLN）、癌胚抗原（CEA）、MUC1等。
  2. 细胞工程：利用第二代或第三代CAR构建T细胞，这些CAR结合了刺激和共刺激信号以增强T细胞的增殖和存活。
  3. 临床试验：开展早期临床试验，评估CAR T细胞的安全性和有效性。

以下是技术路线的流程图：

Mermaid diagram

关键结果和发现 ​

  1. 抗原表达：MSLN在80%的胰腺癌细胞中高表达，且与患者预后相关。
  2. 临床试验结果：在针对MSLN的临床试验中，部分患者在接受CAR T细胞治疗后病情稳定，显示出一定的治疗潜力。
  3. 预处理的重要性：预处理可以通过淋巴耗竭提高CAR T细胞的扩增和持久性，增强其抗肿瘤效果。

主要结论/意义/创新性 ​

CAR T细胞治疗在胰腺癌的应用显示出潜在的前景，尤其是在选择合适的靶抗原和优化治疗方案方面。然而，由于胰腺癌的复杂微环境和免疫抑制特性，治疗效果仍需进一步提升。创新性的策略如结合化疗、免疫检查点抑制剂等可能增强CAR T细胞的疗效。

研究局限性和未来方向 ​

  1. 局限性：当前CAR T细胞治疗在固体肿瘤中的成功率较低，且胰腺癌的免疫微环境复杂，存在免疫抑制。
  2. 未来方向：
    • 继续探索新抗原和组合疗法。
    • 优化CAR T细胞的工程设计，以提高其在肿瘤微环境中的生存能力。
    • 开展更多临床试验以验证疗效和安全性。

综上所述，CAR T细胞治疗在胰腺癌中的研究正处于初期阶段，尽管面临挑战，但其潜在的治疗前景令人期待。

参考文献 ​

  1. Immunohistochemistry of CEA in the human pancreas during development, in the adult, chronic pancreatitis, and pancreatic adenocarcinoma. - G H Albers;G Fleuren;M J Escribano;M Nap - American journal of clinical pathology (1988)
  2. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. - Daniel D Von Hoff;Thomas Ervin;Francis P Arena;E Gabriela Chiorean;Jeffrey Infante;Malcolm Moore;Thomas Seay;Sergei A Tjulandin;Wen Wee Ma;Mansoor N Saleh;Marion Harris;Michele Reni;Scot Dowden;Daniel Laheru;Nathan Bahary;Ramesh K Ramanathan;Josep Tabernero;Manuel Hidalgo;David Goldstein;Eric Van Cutsem;Xinyu Wei;Jose Iglesias;Markus F Renschler - The New England journal of medicine (2013)
  3. The dual adverse effects of TGF-beta secretion on tumor progression. - Joseph A Trapani - Cancer cell (2005)
  4. Mesothelin overexpression promotes mesothelioma cell invasion and MMP-9 secretion in an orthotopic mouse model and in epithelioid pleural mesothelioma patients. - Elliot L Servais;Christos Colovos;Luis Rodriguez;Adam J Bograd;Jun-ichi Nitadori;Camelia Sima;Valerie W Rusch;Michel Sadelain;Prasad S Adusumilli - Clinical cancer research : an official journal of the American Association for Cancer Research (2012)
  5. Prostate stem cell antigen: a Jekyll and Hyde molecule? - Norihisa Saeki;Jian Gu;Teruhiko Yoshida;Xifeng Wu - Clinical cancer research : an official journal of the American Association for Cancer Research (2010)
  6. Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. - Nobuyoshi Hiraoka;Kaoru Onozato;Tomoo Kosuge;Setsuo Hirohashi - Clinical cancer research : an official journal of the American Association for Cancer Research (2006)
  7. Suppression of Tregs by anti-glucocorticoid induced TNF receptor antibody enhances the antitumor immunity of interferon-α gene therapy for pancreatic cancer. - Kouichirou Aida;Reina Miyakawa;Koji Suzuki;Kenta Narumi;Takeshi Udagawa;Yuki Yamamoto;Tatsuya Chikaraishi;Teruhiko Yoshida;Kazunori Aoki - Cancer science (2014)
  8. Changing the course of pancreatic cancer--Focus on recent translational advances. - Milind Javle;Talia Golan;Anirban Maitra - Cancer treatment reviews (2016)
  9. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. - Mark E Dudley;John R Wunderlich;Paul F Robbins;James C Yang;Patrick Hwu;Douglas J Schwartzentruber;Suzanne L Topalian;Richard Sherry;Nicholas P Restifo;Amy M Hubicki;Michael R Robinson;Mark Raffeld;Paul Duray;Claudia A Seipp;Linda Rogers-Freezer;Kathleen E Morton;Sharon A Mavroukakis;Donald E White;Steven A Rosenberg - Science (New York, N.Y.) (2002)
  10. CAR therapy: the CD19 paradigm. - Michel Sadelain - The Journal of clinical investigation (2015)

引用本文的文献 ​

  1. Gene Therapy for Pancreatic Cancer: Specificity, Issues and Hopes. - Marie Rouanet;Marine Lebrin;Fabian Gross;Barbara Bournet;Pierre Cordelier;Louis Buscail - International journal of molecular sciences (2017)
  2. Immune Evasion in Pancreatic Cancer: From Mechanisms to Therapy. - Neus Martinez-Bosch;Judith Vinaixa;Pilar Navarro - Cancers (2018)
  3. Driving CARs on the uneven road of antigen heterogeneity in solid tumors. - Nan Chen;Xiaoyu Li;Navin K Chintala;Zachary E Tano;Prasad S Adusumilli - Current opinion in immunology (2018)
  4. The Role of Mesothelin as a Diagnostic and Therapeutic Target in Pancreatic Ductal Adenocarcinoma: A Comprehensive Review. - Federico Nichetti;Antonio Marra;Francesca Corti;Alessandro Guidi;Alessandra Raimondi;Natalie Prinzi;Filippo de Braud;Sara Pusceddu - Targeted oncology (2018)
  5. Immunotherapy and Prevention of Pancreatic Cancer. - Alexander H Morrison;Katelyn T Byrne;Robert H Vonderheide - Trends in cancer (2018)
  6. Immune Checkpoint Inhibition for Pancreatic Ductal Adenocarcinoma: Current Limitations and Future Options. - Derya Kabacaoglu;Katrin J Ciecielski;Dietrich A Ruess;Hana Algül - Frontiers in immunology (2018)
  7. Gene Therapy for Pancreatic Diseases: Current Status. - Kenya Kamimura;Takeshi Yokoo;Shuji Terai - International journal of molecular sciences (2018)
  8. Low-Dose Radiation Conditioning Enables CAR T Cells to Mitigate Antigen Escape. - Carl DeSelm;M Lia Palomba;Joachim Yahalom;Mohamad Hamieh;Justin Eyquem;Vinagolu K Rajasekhar;Michel Sadelain - Molecular therapy : the journal of the American Society of Gene Therapy (2018)
  9. Therapeutic challenges and current immunomodulatory strategies in targeting the immunosuppressive pancreatic tumor microenvironment. - Chin-King Looi;Felicia Fei-Lei Chung;Chee-Onn Leong;Shew-Fung Wong;Rozita Rosli;Chun-Wai Mai - Journal of experimental & clinical cancer research : CR (2019)
  10. A long way to the battlefront: CAR T cell therapy against solid cancers. - Zhicai Wang;Wei Chen;Xing Zhang;Zhiming Cai;Weiren Huang - Journal of Cancer (2019)

... (41 更多 篇文献)

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