Introduction

The body’s immune system is responsible for fighting foreign bodies such as viruses, bacteria, fungi, parasites and cancers, to ensure freedom from disease, and good health. White blood cells found in the blood are an important component of the immune system. There are four types of WBCs – lymphocytes, neutrophils, eosinophils and monocytes, have a unique protective role

The body’s immune system is constantly on the watch-out for foreign antigens such as cancer cells. A new cancer cell is identified by unique antigens (a kind of protein) that is present on the cell’s surface and acts as its signature. Each type of intruder cell has its own unique signature. When the presence of an intruder cell is detected in the body, T-cells (which are a kind of lymphocyte) proceed to attack those cells. Receptors which are a kind of protein that are present on the surface of T-cells latch on to, or lock on to the antigens on the intruder cell’s surface, and once locked, the T-cell proceeds to destroy the foreign cell. The body quickly starts manufacturing T-cells that possess this particular receptor (or set of receptors) which helps in effectively destroying the intruder cells.

Right from birth and all through his/her life, a person goes through different kinds of intruder attacks. So, over time, a library of intruder antigens, and receptors required to destroy them, are built-up in the immune system. So, the next time there is an attack by the same intruder cell (or even a slight variation), the body has intelligence on how to fight that. This is how one builds immunity over time, after having gone through various ailments. However, at the same time, the person must not be doing anything that harms or hurts the immune system response (through wrong lifestyle and behaviour).

What is CAR-T therapy?

The above process describes the immune response to any intruder cell. However, cancer cells are notorious for hiding from the immune system, to prevent detection and destruction. To do so, they present a range of antigens on their cells’ surface. Some of them may be new and the body may not be able to recognize these antigens. That is, the immune system does not have the required receptors to latch on to them. However, the immune system is able to learn like a human being can, and so by trial and error it starts generating various receptors in an attempt to destroy the intruder cells. This process takes time, which is why cancers take longer to treat. Because, in the meantime, the cancer cells are also not idle and are multiplying rapidly. So once a tumour is detected (through various diagnostic tests), it must be destroyed using medication, radiation, chemotherapy or surgery.

CAR-T therapy is a new approach or form of treatment. In this, the immune-system response is boosted artificially. T-cells are extracted from the patient’s body and genetically modified in a lab. This way, they develop a very specific type of receptor for a very specific type of intruder cell (think of it as a customized response, which eliminates trial and error). The genetically modified T-cells are then allowed to multiply in a lab. Once there is a good enough number of them, they are re-introduced into the patient’s body, in order to fight the cancer cells. CAR-T stands for Chimeric Antigen Response-T cells, which is what the genetically modified T-cells are called now. The therapy derives its name from these cells.

Ailments targeted under CAR-T therapy

CAR-T therapy was first proposed in the 1980s, and has progressed slowly through 2017, after which rapid strides have been seen. So, over time, various types of cancers have been targeted using CAR-T therapy. These include:

• Diffuse large B-cell lymphoma (DLBCL)
• Follicular lymphoma
• Large B-cell lymphoma transformed from follicular lymphoma
• Mantle cell lymphoma
• Adult and paediatric B-cell precursor acute lymphoblastic leukaemia (ALL)
• Multiple myeloma
• Primary mediastinal large B-cell lymphoma
• Aggressive B-cell lymphoma not otherwise specified (NOS)
• High-grade B-cell lymphoma

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Also Read: The different tests required for detecting blood-cancer

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How does the CAR-T treatment happen?

• A catheter is placed in a vein in the patient’s neck or under the collarbone.
• This catheter is connected to a machine that’ll remove the blood from the body gradually, extract WBCs from the blood, after which the RBCs and plasma are returned to the body. This process is called apheresis or leukapheresis.
• T-cells among the WBCs are isolated in the lab. An inactive virus is inserted into T-cells, which gives them instructions to modify themselves.
• The T-cells now start generating chimeric antigen receptors (CAR) and molecules.
• The CA receptors end up on the T-cells’ surface while the CA molecules stay inside the T-cells and send instructions that keep the T-cells active. The T-cells are now called CAR-T cells.
• A small batch of these CAR-T cells are collected and cultured in the lab so that they multiply. This process can take 4-5 weeks of time. The CAR-T cells so produced are frozen and stored. They will be used when the doctors decide to use them on the patient.
• Now, the immune system of the patient may treat these CAR-T cells as intruder cells and start attacking them. To prevent this, and to give a chance for the CAR-T cells to do their job, a process called lympho-deletion is done. This is basically a couple of chemotherapy sessions. This is done because chemotherapy destroys both cancerous and healthy, immune-system cells.
• After the chemotherapy sessions, the CAR-T cells are introduced into the patient’s body through another catheter.
• Once inside the body, receptors on the CAR-T cell latch on to antigens in the cancer cells and proceed to destroy them.
• The CAR T-cells multiply soon, and will continue to monitor the presence of new cancer cells that have the same target antigen, and destroy them whenever they are found. This halts or delays the spread of the cancer.

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Also Read: Lung Cancer Screening Tests – when does one need it?

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After the therapy

Most patients who receive CAR-T therapy will have to stay in the hospital for the entire duration from start to finish, which may be as much as 8 to 10 days, during which time, side-effects, if any, of the therapy are monitored and necessary action taken. In some cases, the CAR-T cells may be introduced into the patient’s body, at home. He/she may have to go to the hospital if and only when side-effects develop. The concerned case-doctors will take a call accordingly.

Kauvery Hospital is globally known for its multidisciplinary services at all its Centers of Excellence, and for its comprehensive, Avant-Grade technology, especially in diagnostics and remedial care in heart diseases, transplantation, vascular and neurosciences medicine. Located in the heart of Trichy (Tennur, Royal Road and Alexandria Road (Cantonment), Chennai (Alwarpet & Vadapalani), Hosur, Salem, Tirunelveli and Bengaluru, the hospital also renders adult and pediatric trauma care.

Chennai Alwarpet – 044 4000 6000 •  Chennai Vadapalani – 044 4000 6000 • Trichy – Cantonment – 0431 4077777 • Trichy – Heartcity – 0431 4003500 • Trichy – Tennur – 0431 4022555 • Hosur – 04344 272727 • Salem – 0427 2677777 • Tirunelveli – 0462 4006000 • Bengaluru – 080 6801 6801

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