Immunotherapy is the treatment of disease by inducing, enhancing or suppressing an Immune Response. Jedd Wolchok MD summed up Immunotherapy just last year in response to Immunotherapy being Science Magazines 2013 Breakthrough of the Year. “10 years ago Immunotherapy was almost in the category of snake oil. A few years ago it was stated that Immunotherapy can work. Now Immunotherapy has entered the main stream.”
James T. Allison, Phd and professor and Chair of Immunology at the MD Anderson Cancer Research Institute (CRI) has received the prestigious Tang Prize, the Louisa Gross Horwitz Prize and the Harvey Prize, all in 2014 for his work on CTLA-4 as an antibody inhibitor in many treatment resistant cancers with amazing survival statistics. Work in CTLA-4 & PD-1 also called “immune check point therapies” are the only two presently approved FDA ImmunoTherapy agents so far.
Specificity. T-cells recognize peptides, which are short chain biological molecules that are produced by every cell category including virus, bacteria, cancer/mutations. T-cells can recognize them and can destroy them, and most importantly they have the following two important elements.
First, Memory. As T-cells destroy pathogens, which are biological or environmental invaders which produce abnormal cells, they go through 3 phases: expansion, contraction and memory. Expansion is when the T-cells multiply to overwhelm the attacker.
Contraction is when they diminish due to program cell death after the attacker is neutralized. Memory is a multiplication of cells that remember the genetic code of the attacker. Memory cells proliferate and circulate through the body standing ready to attack.
Second, Adaptability. Cancerous tumors, viruses and bacteria, can mutate and alter themselves in order to evade various medical therapies. Cancer alone has 9 resistant mechanisms used to trick, hide and survive. So called present “Standard of Care Therapies” which use in large measure synthetically produced drugs frequently harmful to the body, but can’t adapt fast enough to counteract and destroy the mutation capabilities of cancer cells, bacteria and viruses. However, T-cell antigen receptors can. They adapt and respond as quickly as the pathogens, because they can combine and alter themselves as many 10 to the 15th power in different combinations. The stimulation of the T-cells is a natural response of the body’s immune system to the injection of Infeperium. This is the key to why and how of immunotherapy.
So, what is a Biologic or biologic response modifier? According to the United States Food & Drug Administration (FDA) Website in their Questions and Answers Section:
“Biological products include a wide range of products such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living entities such as cells and tissues. Biologics are isolated from a variety of natural sources – human, animal, or microorganism – and may be produced by biotechnology methods and other cutting- edge technologies. Gene-based and cellular biologics, for example, often are at the forefront of biomedical research, and may be used to treat a variety of medical conditions for which no other treatments are available.”
How do biological products differ from conventional drugs?
In contrast to most drugs that are chemically synthesized and their structure is known, most biologics are complex mixtures that are not easily identified or characterized. Biological products, including those manufactured by biotechnology, tend to be heat sensitive and susceptible to microbial contamination. Therefore, it is necessary to use aseptic principles from initial manufacturing steps, which is also in contrast to most conventional drugs.”
Again, according to the FDA, “Biological products often represent the cutting-edge of biomedical research and, in time, may offer the most effective means to treat a variety of medical illnesses and conditions that presently have no other treatments available.”
Therefore, Biologic response modifiers (BRMs) can improve or modify the body’s natural response to infection and disease. BRMs, a drug class of their own, are the newest medications which are based on compounds made by living cells, not synthetic drugs which the body naturally attempts to reject which frequently leads to injury of major organs like the liver and kidneys.
Biological response modifiers (BRMs) are substances that modify immune responses. They can be both endogenous (produced naturally within the body) and exogenous (as pharmaceutical drugs), and they can either enhance an immune response or suppress it.
Some of these substances arouse the body’s response to an infection, and others can keep the response from becoming excessive. Thus they serve as immunomodulators in immunotherapy (therapy that makes use of immune responses), which can be helpful in treating many diseases, such as cancer (where targeted therapy often relies on the immune system being used to attack cancer cells) and in treating autoimmune diseases (in which the immune system attacks the self), such as some kinds of arthritis and dermatitis.
Most BRMs are biopharmaceuticals (biologics), including monoclonal antibodies, interleukin 2, interferons, and various types of colony-stimulating factors (e.g., CSF, GM-CSF, G-CSF). “Immunotherapy makes use of BRMs to enhance the activity of the immune system to increase the body’s natural defense mechanisms against cancer”, whereas BRMs for rheumatoid arthritis aim to reduce inflammation.
An immunomodulator is a substance that either suppresses or activates the body’s immune response. These substances are separated into two groups: immunosuppressants and immune activators. Immunosuppressants inhibit the body’s natural immune response, while immune activators generally condition or reprogram it to target a specific disease-causing agent.
Immunomodulators can be produced in synthetic form or naturally in the body. Cytokines are examples of innate immune mediators. Synthetic versions are available in either immunosuppressant or immune activator forms. A suppressant immunomodulator works by inhibiting the activation of critical immune system agents such as calcineurin and the formation of thymus cells (T-cells) and antibodies. In comparison, an activating immunomodulator uses the process of adaptive immunity to recondition lymphocytes and T-cells to kill known pathogens or tumor cells.
Cyclosporine and methotrexate are commonly used synthetic immunosuppressors. Methotrexate is used in patients with autoimmune ailments. Lupus and rheumatoid arthritis are examples of autoimmune disorders that cause the patient’s body to attack his or her own cells. Eventually the targeted cells and tissue become damaged after repeated attacks.
The process of organ rejection is similar to autoimmune dysfunction, except the immune system targets the transplanted organ rather than the body’s own cells. Organ transplant recipients take suppressant drugs such as cyclosporine, tacrolimus and sirolimus to prevent organ rejection. Nearly all transplant recipients, except a rare few, must adhere to a strict daily regime that involves taking these medications for life. Not taking the medications as prescribed will almost always induce organ rejection, which could lead to death. Due to the medication’s toxic side effects, immunosuppressors should only be used in cases of severe autoimmune dysfunction or organ transplantation.
Immunomodulators that activate the immune system include vaccines and cancer immunotherapy. Vaccines work by exposing the patient to weakened or inactive forms of certain bacteria and viruses. The immune system then adapts by producing antibodies that are programmed to immediately kill the introduced pathogen once it re-enters the body, which is called adaptive immunity.
Cancer immunotherapy is very similar to pathogen vaccination. The difference between the two therapies is the agent in which adaptive immunity is induced. Vaccines use microorganisms, while cancer immunotherapy uses microorganisms and enhanced immune cells. Microorganism-based cancer immunotherapies are used to combat some forms of cervical and liver cancers caused by viruses. A cell-based immunomodulator, on the other hand, uses enhanced immune cells such as cytotoxic T lymphocytes (CTLs), dendritic cells (DC) and natural killer cells (NK cells) to target and destroy the patient’s cancerous cells.