{"title":"Optimising CAR T therapy for the treatment of solid tumors.","authors":"Norhan Mobark, Caroline Malai Hull, John Maher","doi":"10.1080/14737140.2024.2421194","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Adoptive immunotherapy using chimeric antigen receptor (CAR)-engineered T cells has proven transformative in the management of B cell and plasma cel derived malignancies. However, solid tumors have largely proven to be resistant to this therapeutic modality. Challenges include the paucity of safe target antigens, heterogeneity of target expression within the tumor, difficulty in delivery of CAR T cells to the site of disease, poor penetration within solid tumor deposits and inability to circumvent the array of immunosuppressive and biophysical barriers imposed by the solid tumor microenvironment.</p><p><strong>Areas covered: </strong>Literature was reviewed on the PubMed database, excluding occasional papers which were not available as open access publications or through other means.</p><p><strong>Expert opinion: </strong>Here, we have surveyed the large body of technological advances that have been made in the quest to bridge the gap toward successful deployment of CAR T cells for the treatment of solid tumors. These encompass the development of more sophisticated targeting strategies to engage solid tumor cells safely and comprehensively, improved drug delivery solutions, design of novel CAR architectures that achieve improved functional persistence and which resist physical, chemical and biological hurdles present in tumor deposits. Prospects for combination therapies that incorporate CAR T cells are also considered.</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Review of Anticancer Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14737140.2024.2421194","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Adoptive immunotherapy using chimeric antigen receptor (CAR)-engineered T cells has proven transformative in the management of B cell and plasma cel derived malignancies. However, solid tumors have largely proven to be resistant to this therapeutic modality. Challenges include the paucity of safe target antigens, heterogeneity of target expression within the tumor, difficulty in delivery of CAR T cells to the site of disease, poor penetration within solid tumor deposits and inability to circumvent the array of immunosuppressive and biophysical barriers imposed by the solid tumor microenvironment.
Areas covered: Literature was reviewed on the PubMed database, excluding occasional papers which were not available as open access publications or through other means.
Expert opinion: Here, we have surveyed the large body of technological advances that have been made in the quest to bridge the gap toward successful deployment of CAR T cells for the treatment of solid tumors. These encompass the development of more sophisticated targeting strategies to engage solid tumor cells safely and comprehensively, improved drug delivery solutions, design of novel CAR architectures that achieve improved functional persistence and which resist physical, chemical and biological hurdles present in tumor deposits. Prospects for combination therapies that incorporate CAR T cells are also considered.
简介:事实证明,使用嵌合抗原受体(CAR)工程化 T 细胞的采用性免疫疗法在治疗 B 细胞和浆细胞衍生的恶性肿瘤方面具有变革性意义。然而,实体瘤在很大程度上被证明对这种治疗方式具有抗药性。面临的挑战包括缺乏安全的靶抗原、肿瘤内靶点表达的异质性、难以将 CAR T 细胞递送到发病部位、在实体瘤沉积物内穿透力差以及无法绕过实体瘤微环境施加的一系列免疫抑制和生物物理障碍:对 PubMed 数据库中的文献进行了审查,但不包括偶尔出现的无法以开放获取出版物或其他方式获得的论文:在此,我们回顾了在成功应用 CAR T 细胞治疗实体瘤的道路上取得的大量技术进步。这些进步包括:开发了更复杂的靶向策略,以安全、全面地接触实体肿瘤细胞;改进了给药方案;设计了新型 CAR 架构,以提高功能持久性,并抵御肿瘤沉积物中存在的物理、化学和生物障碍。此外,还考虑了结合 CAR T 细胞的综合疗法的前景。
期刊介绍:
Expert Review of Anticancer Therapy (ISSN 1473-7140) provides expert appraisal and commentary on the major trends in cancer care and highlights the performance of new therapeutic and diagnostic approaches.
Coverage includes tumor management, novel medicines, anticancer agents and chemotherapy, biological therapy, cancer vaccines, therapeutic indications, biomarkers and diagnostics, and treatment guidelines. All articles are subject to rigorous peer-review, and the journal makes an essential contribution to decision-making in cancer care.
Comprehensive coverage in each review is complemented by the unique Expert Review format and includes the following sections:
Expert Opinion - a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results
Article Highlights – an executive summary of the author’s most critical points.