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CAR 1

CHIMERIC ANTIGEN RECEPTOR

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CAR 2
Chimeric Antigen Receptor
Chimeric antigen receptors refer to synthetic receptors that are responsible for redirecting
the function, specificity, and metabolism of T cells, and CAR T-cell therapy controls or manages
the natural ability of individual’s immune system to identify and put an end to cancer cells. To
effectively destroy cancer cells, cytotoxic T cells ought to consider them harmful and risky. The
T cells should then be proliferate, activated, and effectively destroy the target cells. CAR T-cell
therapies are associated with a high level of coordination between the manufacturing facility that
generates the CAR T cells and the primary oncology team. The primary oncology team
determines the eligibility of patients for the therapy and offers constant care all through the
treatment process, ranging from prescreening to follow-up. The primary focus of the paper is to
discuss the “chimeric antigen receptor (CAR) T-cell therapy” by identifying the current approved
applications of the treatment, the technology, the future of this therapy, and current challenges
facing this therapeutic approach. The CAR T-cell therapy is an effective approach that is
currently applied in health care to cure cancer but it is associated with a number of challenges
such as macrophage activation syndrome (MAS), “cytokine release syndrome (CRS),” tumor
lysis syndrome, neurologic toxicities, B-cell aplasia, and off-tumor toxicity.
CAR-T cells is among the most promising and advanced types of adoptive T-cell
immunotherapy. Adoptive cell transfer is a concept that was discovered and founded in 1986 by
Steven Rosenberg with the aim of treating patients suffering from cancer using their own
immune cells (Qin et al., 2021). Since then, a lot of advancements have taken place and CAR
technology has been innovated to enhance healthcare efficacy. Currently, the normally used
approach in the health care sector is the “second-generation CAR,” with 4-1BB or CD28
endodomain, portraying important anti-tumor efficacy, while the third generation CAR that

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comprises the two endodomains was considered more toxic. CAR-T treatment has demonstrated
exceptional success in the treatment of B cell malignancies, and individuals who have been
exposed to it have permanent complete remission. Nevertheless, toxicity related to the treatment
as well as antigen loss are issues that require intervention.
Technology of CAR T-Cell Therapy
Chemotherapy, surgery, and radiation treatment are believed to be the foundation of the
treatment of cancer, and progresses in immunology sector have resulted in an in-depth
understanding of the manner in which defenses in a body can be used to treat blood cancers.
CAR T-cell treatment is a category of immunotherapy that uses the T cells of humans to detect
and kill cells causing cancer. T cells are obtained from individuals seeking treatment via
apheresis, a process by which blood is taken out of human body and several blood elements like
platelets, plasma, or white blood cells are removed. The resulting form of blooding is then
infused back into the patient’s body. T cells that are artificially engineered in a laboratory are
capable of identifying proteins that are available on the surface of tumor cells. In the laboratory,
Deoxyribonucleic acid (DNA) is added into the cells, thus giving rise to chimeric antigen
receptors (CARs) on the cells’ surface.
At the treatment center or clinic, the CAR T cells are smelt and then infused into the body
of the patient. Individuals suffering from cancer and who are ready for treatment are offered with
several chemotherapy agents that are designed to reduce the quantity of normal T cells in their
body. This procedure creates room for the CAR T-cells prior to the infusion process. After the
cells get into the bloodstream of the patients, they increase in number and make it possible to
identify and destroy cells that contain the dangerous antigen. The CAR T cells play a key role in
protecting patients from the recurrence of cancer cells after therapy. The cancer cells in human

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blood are eradicated by the CAR T cells and they remain in the victim’s body for a couple of
months after the completion of the infusion process. The therapy is considered effective because
it has led to permanent remissions for certain kinds of blood cancer. CARs are designed in a
modular fashion comprising a hinge region, n extracellular target-binding domain, intracellular
domains, and a transmembrane domain. The transmembrane domain is essential in attaching the
CAR to the cell membrane while the intracellular domains help in transmitting activation signals.
Applications of Chimeric Antigen Receptor (CAR) T-Cell Therapy
The first product of “CAR T-cell” to be approved by “Food and Drug Administration” in
the United States was tisagenlecleucel T that is used for the treatment of individuals below the
age of 25 years who are affected by refractory or relapsed “B-cell acute lymphoblastic leukemia
(B-ALL).” The drug for idecabtagene vicleucel was the most recent approval and it is used in the
therapy for patients experiencing refractory or a relapsed multiple myeloma. However, there are
other five approvals between the above two milestones, for brexucabtene autoleucel,
axicabtagene ciloleucel, lisocabtagene maraleucel for the cure of indolent and aggressive B-cell
non-Hodgkin lymphoma, and lastly, tisagenlecleucel (Gill and Brudno, 2021). The abovementioned products are created from autologous cells obtained from people suffering from
cancer through leukapheresis and they comprise a CAR targeting a lineage antigen that is
associated with the disease. Replication-incompetent lentivirus or retrovirus is used to transduce
CAR transgene into cells and the transgene is made up of costimulatory molecule.
Lympodepleting chemotherapy is also mandated to be used in the therapy, comprising
cyclosphosphamide and fludarabine, before infusion.
The use of CAR-T-cells in the cure of blood cancer has experienced numerous
advan...