CAR-T cells:Early successes in blood cancer and challenges in solid tumors

• 作者: Hassan Dana Ghanbar Mahmoodi Chalbatani Seyed Amir Jalali Hamid Reza Mirzaei Stephan A.Grupp Eloah Rabello Suarez Catarina Rap?so Thomas J.Webster
• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（5）
• 所属期刊栏目: Reviews
• 页码范围: 1129-1147
• 页数: 19页
• 语种: 英文

摘要

New approaches to cancer immunotherapy have been developed,showing the ability to harness the immune system to treat and eliminate cancer.For many solid tumors,therapy with checkpoint inhibitors has shown promise.For hematologic malignancies,adoptive and engineered cell therapies are being widely developed,using cells such as T lymphocytes,as well as natural killer(NK)cells,dendritic cells,and potentially others.Among these adoptive cell therapies,the most active and advanced therapy involves chimeric antigen receptor(CAR)-T cells,which are T cells in which a chimeric antigen receptor is used to redirect specificity and allow T cell recognition,activation and killing of cancers,such as leu-kemia and lymphoma.Two autologous CAR-T products have been approved by several health authorities,starting with the U.S.Food and Drug Administration(FDA)in 2017.These products have shown power-ful,inducing,long-lasting effects against B cell cancers in many cases.In distinction to the results seen in hematologic malignancies,the field of using CAR-T products against solid tumors is in its infancy.Tar-geting solid tumors and trafficking CAR-T cells into an immunosuppressive microenvironment are both significant challenges.The goal of this review is to summarize some of the most recent aspects of CAR-T cell design and manufacturing that have led to successes in hematological malignancies,allowing the reader to appreciate the barriers that must be overcome to extend CAR-T therapies to solid tumors suc-cessfully.