EDEN IAS

CAR T CELL THERAPY

Why in the news CAR T-Cell Therapy?

The Central Drugs Standard Control Organisation (CDSCO) conceded market authorization for NexCAR19, India’s first natively created Vehicle White blood cell treatment Car t cell, to ImmunoACT, an organization hatched by IIT Bombay. This makes it ready for the business to send off this treatment in India, where it is normal to be accessible to disease patients at a 10th of the expense abroad.

What are CAR T cells?

In the field of biology, receptor proteins call chimeric antigen receptors (CARs)—also refers to as chimeric immunoreceptors, chimeric T cell receptors, or artificial T cell receptors— modify to allow T cells to target a particular antigen. The receptors chimeric because they serve as a single receptor to perform both T cell activation and antigen-binding tasks.

To cure cancer, T cells modifies with CARs use in CAR T cell therapy. T cells have been alter to identify and eliminate cancer cells. Traditionally, patients’ T cells are extracts, genetically modifies, and then infuse with the resultant CAR T cells to combat their cancers.

CAR T cells can be produce allogeneically from donor T cells or autologously from T cells in the patient’s blood. Following their isolation, these T cells undergo genetic engineering to produce a particular CAR using a vector generates from an HIV-like lentivirus (see Lentiviral vector in gene therapy). The T cells are programs by the CAR to target an antigen on the surface of the tumor cell. CAR T cells use for safety.

History of Car t cell therapy.

In 1987, Yoshihisa Kuwana et at Fujita Health University and Kyowa Hakko Kogyo, Co. Ltd. in Japan described the first chimeric receptors that combined parts of an antibody and the T cell receptor. Gideon Gross and Zelig Eshhar at the Weizmann Institute in Israel described them independently in 1989. These early methods (called “T-bodies” initially) coupled the constant domains of TCR-α or TCR-β proteins with an antibody’s specificity for binding to a variety of targets.

Production of CAR T cells.

Isolating T cells from human blood is the first stage in the creation of CAR T-cells. Both the patient’s own blood (autologous treatment) and the blood of a healthy donor (allogeneic treatment) can be use to produce CAR T-cells. The only difference between the two scenarios is the initial blood donor selection. The manufacturing procedure remains the same.

CAR T CELL

Applications:

Cancer

T cells genetically engineered to express chimeric antigen receptors specifically directed toward antigens on a patient’s tumor cells, then infused into the patient where they attack and kill the cancer cells.[28] Adoptive transfer of T cells expressing CARs is a promising anti-cancer therapeutic because CAR-modified T cells can be engineered to target potentially any tumor-associated antigen.

Early CAR Tcell research has focused on blood cancers. The first approved treatments use CARs that target the antigen CD19, present in B-cell-derived cancers such as acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). There are also efforts underway to engineer CARs targeting many other blood cancer antigens, including CD30 in refractory Hodgkin’s lymphoma; CD33, CD123, and FLT3 in acute myeloid leukemia (AML); and BCMA in multiple myeloma.

Autoimmune disease of car t cells

There are other possible applications for this technology, even though the majority of CAR Tcell research concentrates on developing CAR T cells that are capable of eliminating a particular cell population (such as CAR T-cells that target lymphoma cells). Tolerance to antigens can also be mediated by T cells. When paired with a CAR, a regulatory T cell may be able to provide tolerance to a particular antigen, which may be useful in organ transplantation or rheumatologic conditions such as lupus.

Side effects and challenges

The introduction of CAR T-cells into the body can have major side effects, including neurological toxicity and cytokine release syndrome. Little information is available regarding the long-term consequences of CAR T-cell therapy because it is a relatively new treatment. Long-term patient survival and pregnancy difficulties in female CAR T-cell recipients remain unresolved concerns. Because the CAR is manufactured using a foreign monoclonal antibody, which incites an immune response, anaphylaxis could be a side effect.

Additionally, it is improbable that the CAR gene inserted by the viral vector into an oncogene or tumor suppressor in the host T cell’s genome will cause the modified CAR T-cells to undergo insertional mutagenesis and develop into malignant cells. Certain lentiviral (LV) vectors are more dangerous than retroviral (RV) vectors. Both, though, can be carcinogenic. To gain a deeper comprehension of CAR T-cell activity and persistence in vivo, a genomic sequencing study of CAR insertion sites in T cells has been established.

cytokine release syndrome (CRS)

The most common Issue after treatment with CAR T-cells is cytokine release syndrome (CRS), a condition in which the immune system is activated and releases an increased number of inflammatory cytokines. The clinical manifestation of this syndrome resembles sepsis with high fever, fatigue, myalgia, nausea, capillary leakages, tachycardia and other cardiac dysfunction, liver failure, and kidney impairment

Neurological toxicity

CAR T-cell therapy is also frequently linked to neurological toxicity. The underlying mechanism is unclear and may or may not be related to CRS. Clinical manifestations include delirium, expressive aphasia—a partial loss of language comprehension in speech—lowered alertness (obtundation), and seizures.

CAR T cell therapy in India

Is India’s indigenous CAR-T cell therapy any more or less effective than CAR-T cell therapies abroad?

Laboratory and animal studies have shown a unique quality of this product. Specifically, it leads to significantly lower drug-related toxicities. It causes minimal damage to neurons and the central nervous system, a condition known as neurotoxicity. Neurotoxicity can sometimes occur when CAR-T cells recognize the CD19 protein and enter the brain, potentially leading to life-threatening situations

BENEFITS TO INDIA of car t cells

Treatment of Hematologic Cancers: CAR T-cell therapy has demonstrated remarkable success in treating certain types of hematologic cancers, such as B-cell lymphomas and leukemias. Since these cancers are prevalent in India, where the burden of blood cancers is significant, the therapy offers a potential breakthrough in treatment options.

Alternative for Relapsed or Refractory Cases: CAR T-cell therapy provides an alternative for patients who have relapsed or are refractory to conventional treatments like chemotherapy and radiation. In India, where access to certain advanced treatments may be limited, CAR T-cell therapy offers hope for those who have exhausted standard treatment options.

Reduced Reliance on Transplants: In cases where stem cell transplants are not feasible or available, CAR T-cell therapy can offer an effective treatment option. This is particularly relevant in India, where challenges related to donor availability and compatibility can limit the widespread use of transplant-based treatments.

Potential for Cost-Effective Solutions: While CAR T-cell therapy is currently an expensive treatment, advancements and increased production could lead to cost reductions over time. If the therapy becomes more cost-effective, it could become a viable option for a larger segment of the population in India.

Advancements in Biotechnology and Research Collaboration: The development and implementation of CAR T-cell therapy in India would likely involve collaborations with international research institutions and pharmaceutical companies. This could contribute to advancements in the field of biotechnology and healthcare research in the country.

Improved Healthcare Infrastructure: The introduction of CAR T-cell therapy could drive improvements in healthcare infrastructure, fostering the development of specialized treatment centers and expertise in cellular therapies. This, in turn, could have broader positive implications for the overall healthcare system in India.

Boost to Biotechnology Industry: Adopting CAR T-cell therapy could stimulate growth in the biotechnology and pharmaceutical sectors in India. It might encourage investments in research and development, leading to the creation of more jobs and expertise in cutting-edge medical technologies.

CONCLUSION OF CAR T CELL

Despite these potential benefits, it’s essential to acknowledge the challenges, including the high cost, logistical issues related to transportation of cells, and the need for specialized infrastructure and trained personnel, taking into account the side effects associated with it. Successful implementation would require a comprehensive approach involving healthcare providers, policymakers, researchers, and industry stakeholders.

Sources: indian express