The Role of Chimeric Antigen Receptor-T Cell Therapy in the Treatment of Hematological Malignancies: Advantages, Trials, and Tribulations, and the Road Ahead.

Content Provider	Europe PMC
Author	Rohit Reddy, Sai Llukmani, Adiona Hashim, Ayat Haddad, Dana R Patel, Dutt S Ahmad, Farrukh Abu Sneineh, Majdi Gordon, Domonick K
Editor	Muacevic, Alexander Adler, John R
Copyright Year	2021
Abstract	Immunotherapy is the upcoming trend in cancer treatment. Traditional cancer treatment methods include surgical resection, radiotherapy, chemotherapy, small molecule targeted drugs, monoclonal antibodies, and hematopoietic stem cell transplantation (HSCT). Surgical resection is useful for early-stage patients but not for metastatic cancer cells; radiotherapy and chemotherapy are more common but produce substantial damage to normal tissues and have poor selectivity. Targeted drugs, including monoclonal antibodies, have better comprehensive efficacy but can also encourage gene mutation of tumor cells and drug tolerance. HSCT is effective, but choosing a donor is often difficult, and the graft is also prone to rejection. Thus, chimeric antigen receptor (CAR)-T cell therapy, a form of cellular/adoptive immunotherapy, is at the forefront of cancer therapy treatments due to its sustained remission, fewer side effects, and a better quality of life. CAR-T cell therapy involves genetically modifying the T cells and multiplying their numbers to kill cancer cells. This review article gives an insight into how the CAR-T cells have evolved from simple T cells with modest immune function to genetically engineered robust counterparts that brought great hope in the treatment of hematological malignancies. Much research has been undertaken during the past decade to design and deliver CAR-T cells. This has led to successful outcomes in leukemias, lymphomas, and multiple myeloma, paving the way for expanding CAR therapy. Despite tremendous progress, CAR-T cell therapies are faced with many challenges. Areas for improvement include limited T cell persistence, tumor escape, immunosuppressive components in the tumor microenvironment, cancer relapse rate, manufacturing time, and production cost. In this manuscript, we summarize the innovations in the design and delivery of CAR technologies, their applications in hematological malignancies, limitations to its widespread application, latest developments, and the future scope of research to counter the challenges and improve its effectiveness and persistence.
Journal	Cureus
Volume Number	13
DOI	10.7759/cureus.13552
PubMed Central reference number	PMC8007123
Issue Number	2
PubMed reference number	33815972
e-ISSN	21688184
Language	English
Publisher	Cureus
Publisher Date	2021-02-25
Publisher Place	Palo Alto (CA)
Access Restriction	Open
Subject Keyword	adoptive immunotherapy hematological malignancies side effects of car therapies car-t cells in hematological malignancies car-t cell design next generation car-t cells immunotherapy and hematological malignancies car-t cell therapy safety strategies in car therapy fda approved car therapies
Content Type	Text
Resource Type	Article
Subject	Medicine