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New Approach Towards Cancer Treatment: Immuno-oncology

What is Cancer?

Cancer is a disease characterized by the uncontrollable growth of body cells. These mutated cells grow and attack the other normal functioning cells of the body. Cancers can start at any part of the body. The tumor may be non-cancerous (benign) which does not affect the normal function cells of the body or may be malignant (cancerous). Cancerous cells grow in absence of a signal telling them to grow and also ignore the signal which tells them to undergo apoptosis, also they can hide from the immune system.

The Promise of Immuno-oncology

Cancer immunotherapy also called Immuno-oncology is a method in which the body uses its power to prevent, treat and eliminate cancer. Immunotherapy depends on memory. This therapy enables the immune system to boost, recognize and attack the specific cancer cells, and also provides the body with additional components to enhance the immune response.

Cancer immunotherapies come in a variety of forms including targeted antibodies, cancer vaccines, adoptive cell transfer, tumor-infecting viruses, checkpoint inhibitors, cytokines, and adjuvants.

Immuno-oncology therapy works differently than conventional chemotherapy. It unleashes indiscriminate, static, and lethal direct attacks on all cells – malignant and normal – in hopes of damaging the cancer cells more than the host cells.

Basic Tumor Immunology

  • The Biology of Cancer

In recent years, researchers are looking for combining chemotherapy with immune-oncology therapy. Here, the goal is to not only clear the cancer cells but also to optimize immunologic clearance, which may allow for lower chemotherapy dosing.

There are mutations in cells which causes them to become defective. These mutations are of two types:

  1. the dominant type which results from an abnormality in one gene in a pair. This mutated gene produces a defective protein that switches on the growth factor receptor present on the cell surface, even when no growth factor is present. Thus cells constantly divide and this gain of the function gene is called an oncogene.
  2. Another type of mutation present is the recessive mutation. This results from damage to both the genes. E.g. the gene p53 produces a protein that turns off the cell cycle and controls cell growth. The primary function of p53 is to repair or destroy the defective cells, which helps in controlling cancer. This is called the tumor suppressor gene. If one gene is mutated in p53, the other gene will control growth. If both the genes are “off”, the cell division is no longer under control.
  • Immune Recognition

The innate immune system is universal and is an ancient form of host defense against infection. These receptors can distinguish between self and nonself antigens based on memory. Toll-like receptors play a major role in identifying pathogens and initiate various immune and inflammatory responses. When these Toll-like receptors are activated, it activates signaling pathways that induces antimicrobial genes and stimulates inflammatory cytokines.

  • Inducing Immune Response: CD8+ T Cells

CD8 cells are the major cell population of the adaptive immune system. The defining characteristic of CD-8 cells T lymphocytes is that it is composed of millions of clones. Each of the T cell receptors can recognize a limited number of peptides displayed on the cell surface-bound to Major histocompatibility complex 1 (MHC1). CD-8 cells are involved in killing virus-infected cells and produce antiviral cytokines such as interferon-gamma. This is how CD-8 T-cells contribute to resisting primary and secondary viral infections.

CD4+T cells and CD8+ T cells form the majority of T lymphocytes. CD4+T cells, once activated, differentiate into distinct effector subtypes. It plays a major role in the activating immune cell responses such as B lymphocytes, cytotoxic T cells. CD4+ T cells also activate non-immune cells play a major role in immune responses by secreting cytokines.

  • Immune Response of NK Cells

NK cells or natural killer cells are activated in response to interferons or macrophage-derived cytokines. They serve to prevent viral infection by secreting interferon-alpha and interferon-gamma.

  • Immune Evasion: T Cells

T lymphocytes play a key role in eliminating virus-infected cells. They detect the virus-derived peptides displayed at the cell surface in the context of MHC class I molecules. This system of recognition is a target for immune evasion.

Checkpoint Blockade:

Checkpoint blockade immunotherapy is an innovative treatment that uses medication known as immune checkpoint inhibitors which are used to treat several types of cancer. Specifically, this medication help the body’s immune system to recognize cancer cells. Cancer cells tend to avoid these checkpoints and continue to spread. Checkpoint blockade immunotherapy has shown efficacy against a variety of malignancies including melanoma, lung cancer, kidney cancer, bladder cancer, and Hodgkin’s lymphoma.

CAR T and Other Novel Therapies

Chimeric Antigen T cells or CAR T cells are T cells that are genetically engineered to produce an artificial T cell receptor that target specific proteins. These receptors are chimeric as they combine antigen-binding and T cells activation functions into a single receptor. The idea behind CAR T therapy is to identify the cancer cells and target them more effectively.

Scientists isolate the T cells from people, genetically alter them then infuse the resulting CAR T cells into the patients to attack their tumors. CAR T cells can be obtained from a patient’s own blood (autologous) or they can be isolated from a healthy donor. For safety, CAR T cells are engineered to be specific to an antigen expressed on a tumor that is not expressed on healthy cells.

The Future of Immuno-oncology

Immunotherapy is a new treatment for cancer, including the cancer of the bladder, kidney, and other organs. Immunotherapy not only targets the cancer cells but also spares healthy cells to extend survival and improve the patient’s quality of life. At present immunotherapy is available for a few types of cancer but still, researchers are focusing in targeted immunotherapy for all cancers types.

Author

Ritika Gupta

Ritika Gupta is an MPharm. graduate who is keen on spreading awareness about various unexplored medical fields through her writings.

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