T-Cell (CAR-T) Therapy

 






T-Cell (CAR-T) Therapy

Chimeric Antigen Receptor (CAR) T-cell therapy involves genetic modification of a patient’s autologous T-cells to express a CAR specific for a tumor antigen.

It is followed by ex vivo cell expansion and re-infusion back to the patient.   

CARs are fusion proteins of a selected singlechain fragment variable from a specific monoclonal antibody and one or more T-cell receptor intracellular signaling domains.


This T-cell genetic modification may occur either via viral-based gene transfer methods or non-viral methods, such as DNA-based transposons, CRISPR/ Cas9 technology or direct transfer of in vitro transcribed-mRNA by electroporation. 

CAR_  T Cell Theropy death rates 

CAR T-cell therapy, also known as chimeric antigen receptor T-cell therapy, is a type of immunotherapy that uses modified T-cells from a patient's own immune system to target and destroy cancer cells. While CAR T-cell therapy has shown promising results in treating certain types of cancer, it can also have severe side effects, including cytokine release syndrome (CRS) and neurologic toxicities.


The death rate associated with CAR T-cell therapy can vary depending on several factors, such as the type and stage of cancer being treated, the specific CAR T-cell therapy being used, and the overall health of the patient. Generally, the death rate associated with CAR T-cell therapy is low, but it is not without risks.


In clinical trials and real-world data, the reported death rates vary between studies. According to a study published in the Journal of Clinical Oncology in 2019, the death rate associated with CAR T-cell therapy ranged from less than 1% to about 10%, depending on the type of cancer being treated. 


It is important to note that CAR T-cell therapy is typically reserved for patients with advanced or refractory cancers who have exhausted other treatment options. Therefore, the benefits of CAR T-cell therapy in terms of potential curative effects often outweigh the risks for these patients.


Before considering CAR T-cell therapy, patients and their healthcare providers carefully assess the potential risks and benefits based on an individual's specific circumstances. Close monitoring and management of side effects are crucial to minimizing risks and improving patient outcomes.

T-Cell (CAR-T) Therapy

Why in the news? 


Recently, the Central Drugs Standard Control Organisation (CDSO) approved the Indigenous Chimeric Antigen Receptor T cell (CAR-T cell) therapy. More in News

 ●The therapy is called NexCar19, a type of CAR-T and gene therapy developed indigenously in India by ImmunoACT, which is a company incubated at IIT Bombay. 

●It will treat lymphoma and Leukaemia (Blood Cancer). 

● India is now one of the first developing countries to have its indigenous CAR-T and gene therapy platform. 

Lymphocytes: T-cell vs.


 B-cell Lymphocytes are a type of White Blood Cells (WBCs) that circulate in blood and are part of the immune system.

 There are two main types of lymphocytes: T cells and B cells. 


Characteristics

T_ cell 

Function: T cells are direct fighters of foreign invaders and also produce cytokines, which are biological substances that help activate other parts of the immune system. (Attacks infected cells)

 Origin and Maturation :Originate from stem cells in the bone marrow but  mature in the thymus gland.

 Immunity: Play a central role in cell-mediated immunity

B_ Cell 

 Function:   B cells produce antibody molecules that can latch on and destroy invading viruses or bacteria. (Attacks foreign bodies outside the cells)

 Origin and Maturation:  Originate and mature in the bone marrow

 Immunity:  Responsible for humoral immunity.

About NexCAR19 

●The therapy is designed to target cancer cells that carry the CD19 protein. 

 CD-19 is a biomarker (or flag) for B lymphocytes (or B-cells) and can be utilised as a target for leukaemia immunotherapies. 

(i) A Biomarker is a measurable and assessable indicator, often a molecule or characteristic, that provides information about a biological process, condition, or response to a treatment. 

● This therapy is for people with B-cell lymphomas (blood cancer) who don’t respond to standard treatments like chemotherapy, leading to relapse or recurrence of the cancer






CAR-T Therapy vs. Chemotherapy 

Aspect

CAR-T Therapy

 Mechanism of Action :   Genetically modifies patient's T cells to target  cancer 

 Precision: Highly precise, targeting specific cancer cells
 Treatment duration: Typically, a single infusion or a few treatments 

  Personalization: Individualized treatment based on patient's own cells 

Chemotherapy

 Mechanism of Action:   Uses drugs to kill rapidly dividing cells, including cancer

 Precision:  Non-specific, affecting both cancer and healthy cells

 Treatment duration:  Multiple cycles, often over an extended period

 Personalization:  Standardized treatments, less personalized approach



Challenges in adoption 


Cytokine Release Syndrome ( CRS):  It occurs when the proliferation of CAR T-cells leads to the release of abundant cytokines into the bloodstream, triggering an intensified immune system response.

  ● Neurological  Toxicity  : Some patients may experience neurotoxicity, leading to confusion, seizures, or other neurological issues, often associated with CRS. 

 ● Limited Applicability  : CAR-T therapy has primarily been successful in treating certain blood cancers, like leukaemia and lymphoma, and its effectiveness in solid tumours is an ongoing area of research. 

 ● High Cost :  The personalized and complex nature of CAR-T therapy contributes to its high cost, limiting its accessibility to a larger population. 

 ● Patient Eligibility  : Not all patients are eligible for CAR-T therapy, and factors such as age, overall health, and the presence of certain pre-existing conditions can impact eligibility. 



Way forward 

  Enhance Safety profiles : Continuous research to improve the safety profile of CAR-T therapy, minimizing severe side effects such as cytokine release syndrome (CRS) and neurotoxicity. 

Global Collaboration  : Encourage international collaboration and data-sharing to accelerate research, share best practices, and facilitate the global advancement of CAR-T therapy. 

 Enhancing Assessibility : By developing Standard Operating Procedures (SOPs) for its application and integrating it into prevalent insurance packages.

  Intensive Research: Invest in research to broaden the applications of CAR-T therapy, exploring its effectiveness in treating additional types of cancer beyond Blood cancer


















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