HEALTHWATCH
Innovative weapon in cancer therapy
DR. K. GOVINDBABU
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Monoclonal antibodies represent a novel biological therapy to detect or treat cancer.
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New approaches: There's hope for the future.
CANCER is a leading cause of death globally. The treatment of cancer is increasingly becoming multidisciplinary. Several treatment modalities are used concurrently, or in sequence.
Depending on a variety of factors, including the type of cancer, the stage of its progression and the goal of treatment, one or more treatment modalities may be employed. These may include surgery, radiation therapy, chemotherapy and/or biological therapy.
Highly specific
Biological therapy is largely by way of immunotherapy, which is increasingly gaining acceptance as a novel approach to cancer treatment with a synergistic effect when combined with chemo and/or radiation therapy. What sets it apart from other therapies is that it works by using the body's own defence mechanisms to fight the disease, either directly or indirectly.
Biological therapies employ natural body substances or drugs made from natural body substances to identify and attack specific cancer cells without harming normal cells. Biological therapeutics is highly specific as they are designed to target specific tumour markers.
With tumour specific targeting, there is an increasing recognition that cancers, even if they appear to be of the same type, are in fact highly diverse, and two people seemingly afflicted by the same type of cancer might actually require very different treatments. In effect, biological therapy represents a shift in focus, from "uniform" to more "individualised" treatment of cancer.
Monoclonal antibodies or MAbs represent one of the novel biological therapies available today to detect or treat cancer. They belong to a family of substances called biological response modifiers whose prime job is to restore, direct or boost the body's ability to fight cancer.
How they work
Understanding how MAbs work would require some quick insights into the functioning of the body's immune system. The immune system is a complex network of cells and organs that work in concert to defend the body against attacks by "foreign" invaders.
An important part of the immune system is proteins called antibodies. When harmful microorganisms, which include bacteria, viruses, and parasites, breach the body's defence mechanisms; B-cells in the immune system produce antibodies that help destroy them.
Chemical substances, called antigens, are found on the surface of cancer cells. The antibodies recognise these cancer or abnormal cells and latch on to their antigens. Each antibody has a particular antigen with which it fits, like a key would to a lock. The tagged or labelled cancer cells are then destroyed by the antibodies themselves or other cells in the immune system, alerted through chemical signals. What if the immune system's response is less than optimal? What if the entire immune system breaks down? The short answer: cancer may develop. That's where biological therapies come in, helping to repair, stimulate, or boost the immune system.
Therapeutic agents
MAbs are created in the laboratory from a single clone of a B-cell, the type of cells of the immune system that make antibodies. Different antibodies are needed for different cancers. For instance, MAbs that work on cells for ovarian cancer will have no effect at all for a B-cell lymphoma.
Over the last 30 years, MAbs have progressed from being from tools in basic research to diagnostic agents and, with humanisation, to the level of therapeutic agents. Monoclonal antibody therapy is a form of passive immunotherapy because the antibodies are made in large quantities outside the body (that is, in the lab) rather than by a person's immune system.
The therapy, therefore, does not require the patient's immune system to take an "active" role in fighting the cancer.
Currently, two types of MAbs are used in cancer treatment: naked and conjugated. Naked MAbs are those without any drug or radioactive material attached to them. They work in various ways: some mark the cancer cells for destruction by the immune system, others latch onto receptors, or antigen sites, preventing other molecules that stimulate growth of cancer cells from binding on to these sites.
Conjugated MAbs, on the other hand, are those joined to a chemotherapy drug, radioactive particle, or a toxin. They home in on cancer cells and deliver their "cargo" that destroys the tumours, in the process minimising damage to normal cells. MAbs can also be used to carry radioisotopes that may help diagnose certain types of cancer.
Use of monoclonal antibody therapy has already been approved for certain types of cancer. With the discovery of more cancer-associated antigens, more and more cancers are set to come under its fold. If clinical trials continue to demonstrate its efficacy, it is quite possible that this therapy might emerge as a standard, stand-alone treatment for some types of cancer. In combination with chemotherapy and/or radiotherapy, the therapeutic impact is clearly seen to be synergistic in significantly extending survival rates.
The writer is Associate Professor, Senior Consultant, Medical Oncologist, Kidwai Memorial Institute of Oncology, Bangalore.
What is targeted immunotherapy?
With targeted immunotherapy gaining currency, chemotherapy, which dominated cancer treatment for decades, is losing some of its shine. While chemotherapy has several merits, its main disadvantage is that it treats the entire body. Result? Both cancerous and normal cells get killed, leading to several undesirable toxic effects.
Chemotherapy and radiotherapy can also weaken immunity by reducing the number of white blood cells, which defend the body against infectious disease and foreign materials, produced in the bone marrow.
Targeted immunotherapy, in contrast, takes a different approach to cancer treatment. Cancer is characterised by uncontrolled, abnormal growth of cells. The resulting mass, or tumour, invades and destroys surrounding normal tissues. Targeted immunotherapy essentially arrests this phenomenon by blocking the chemical signals that brings this about. And since it is directed as specific pathways and mechanisms that cause the disease, it is far more effective and certainly less toxic than chemotherapy.
If one may use an analogy, chemotherapy represents a "cluster bomb" approach to cancer treatment, while targeted therapy is more like a "missile".
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