CAR-T cell therapy: The future mainstay of cancer treatments

Basics of cancer

  • As we have seen cell division through mitosis is the way living organisms grow in which 1 cell becomes 2, 2 becomes 4, 4 becomes 8, 8 becomes 16 and so on.
  • If this process goes on forever unchecked, cell division reaches dangerous levels which is not desirable.
  • Thus, in order to maintain balance (homeostasis), cells have adapted themselves to a process called apoptosis which is also called programmed cell death.
  • This process starts by severe damage to DNA which is signaled to cell after which the whole cell destroys itself. The left-over cell mass, after death, are eaten by phagocytes (cell-eating cells).
  • Cancer is a condition of unrestrained cell growth and division due to absence of apoptosis/programmed cell death.
  • Cancer occurs when some disruption of the DNA in a normal cell interferes with the cell’s ability to regulate cell division. DNA disruption can be caused by chemicals that mutate DNA or by sources of high energy such as X rays, the sun, or nuclear radiation, even infection by viruses.

Cause of cancer

  • Most cancer is caused by mutations in a cell’s DNA that disrupt the normal processes that control and regulate the cell cycle.
  • More specifically, the cancer-causing mutations seem to affect two different types of genes: those that stimulate cell growth and those that restrain it.

Difference between cancer cells and normal cells

  • Most normal cells divide until they touch other cells or collections of cells (tissues). At that point, they stop dividing. Normal human cells can divide 80–90 times.
  • Cancer cells on the other hand ignore the signal that they are at high density and continue to divide indefinitely. 
  • Cells are normally held together by adhesion molecules, proteins within cell membranes. Cancer cells when grouped together like this form a tumor.

Types of cancer

  • Two different types: benign and malignant.
  • Benign tumors, such as many moles, are just masses of normal cells that do not spread. They can usually be removed safely without any lasting consequences.
  • Malignant tumors, on the other hand, are the result of unrestrained growth of cancerous cells.
  • They turn in to tumors that shed and spread cancer cells.
  • The cancer cells after some time separate from a tumor and invade the circulatory system and lymphatic pathways, then spread to different parts of the body where they can cause the growth of additional tumors.

How does cancer kill you?

  • Cancer cells are not toxic as they are our own body cells.
  • The problem arises as tumor gets larger, it uses up nutrients and energy, takes up more space, and presses against neighboring cells and tissues.
  • Eventually, it blocks other cells and tissues from carrying out their normal functions and kill them.

Treatment of Cancer

  • To treat cancer, the rapidly dividing cells must be removed surgically or killed, or their division slowed down. 
  • Killing and slowing down are done in two ways: by chemotherapy and by radiation.”

Chemotherapy

  • Drugs that interfere with cell division are administered, slowing down the growth of tumors.
  • Because these drugs interfere with rapidly dividing cells throughout the body they disrupt normal cells too, thereby causing extreme fatigue as it reduces the rate at which red blood cells are produced.
  • By interfering with the division of bone marrow stem cells, chemotherapy also reduces the production of platelets and white blood cells and thus increases bruising and bleeding, as well as a susceptibility to infection.
  • The rapidly dividing cells within hair follicles are also affected by chemotherapy (and radiation). Consequently, many people lose their hair when undergoing treatments.

Radiation

  • Also works by disrupting cell division, but it is more targeted.
  • It directs high-energy radiation only at the part of the body where a tumor is located.
  • However, the radiation process is not perfect, and nearby tissues are often harmed.

CAR T-cell therapy: Future of cancer treatment

  • CAR T cell therapy involves genetically modifying our immune cells called T-cells to attack and kill cancer cells.
  • Normally during an infection one type of T-cells attack and kill pathogens.
  • In order to do so, T-cells have to identify the foreign cells.
overview of CAR T-cell therapy: Future of cancer treatment
  • It is the job of B-cells to identify the pathogen and signal other immune cells to do their job.
  • To do it make an image of the pathogen and present it to the immune system. This is called antigen.
  • Now because the cancer cells are not foreign cells B-cells cannot recognize them as foreign bodies and hence cannot present it to the immune system(T-cells) as enemy cells.
  • Alternately if we can genetically alter T-cells to recognise the cancer cells, it will kill it. This is what CAR T-cell therapy does.
  • Under this, T-cell is genetically modified, using CRISPR system, to recognize the image of cancer cell (chimeric antigen receptor).

Potential limitations of CAR T-cell therapy

  • CAR T-cell therapy could induce immune response like increased cytokine release which can lead to fever, low blood pressure, and organ damage.
  • Further CAR T cell therapy are best suited for blood cancers and may not be effective for all types of cancer.
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