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Pembrolizumab: A New Path for Mesothelioma Treatment

What is Pembrolizumab?

PembrolizumabPembrolizumab or Keytruda is a drug manufactured by Merck Pharmaceuticals. Keytruda was given accelerated approval by the U.S. Food and Drug Administration for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) on October 2, 2015. Keytrunda is a programmed death receptor-1 (PD-1) blocking antibody.   It is a humanized monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 with potential immune checkpoint inhibitory and antineoplastic activities. The NSCLC tumor must express programmed death ligand 1 (PD-L1) as determined by an FDA approved test, with disease progression on or after platinum-containing chemotherapy.   Patients whose cancer has certain gene mutations should receive this drug only after their disease got worse after treatment with FDA- approved therapy for the gene mutation. Pembrolizumab is also approved for melanoma that cannot be removed by surgery or that has metastasized.

How does Pembrolizumab work with the Immune System?

Pembrolizumab works with your immune system in a very specific way. It will not work with all cancers. At this point Clinical Trials are being conducted for its indications in other cancers. The cancers that Pembrolizumab is being trialed on include bladder, breast, colorectal, esophageal, gastric, head and neck, hematology, lung, and melanoma.

Pembrolizumab and Mesothelioma

Mesothelioma tumors are all different.   By finding and understanding the proteins that the tumor secretes it is hoped that the drug can target the immune system cancer-specific antigens. Once targeted the drug will then activate the immune system to seek out the cancer targets. Research is continuing in the sustainability of the treatment. If sustainable, is it a cure?   This is all research that needs clinical trials to follow patients over time and measure the results.

Pembrolizumab is administered intravenously. The dose is 2mg per kilogram. A person weighing 170 pounds would receive 155mg. It would be infused intravenously over 30 minutes every 3 weeks.

Side effects include fatigue, decreased appetite, dyspnea- and cough.

Adverse reactions include immune mediated pneumonitis, colitis, hepatitis, nephritis.

More information can be found about Pembrolizumab on www.cancer.gov/about-cancer/treatment/drugs/pembrolizumab

Pembrolizumab and Mesothelioma Clinical Trials

Presently there are 3 Clinical Trials listed on www.ClinicalTrials.gov involving mesothelioma and Pembrolizumab. We strongly encourage you to consider these clinical trials. Immunotherapy can be a promising treatment option against mesothelioma. The only way for this potentially exciting treatment option to be proven for mesothelioma is participation in a Clinical Trial.

The Immune System, Immunotherapy and Mesothelioma

immunotherapyThere are new ads on TV announcing new, exciting drugs for the treatment of certain types of lung cancer. The ads show people that are with their families seeing the news of another option for therapy. What are they talking about? How does it relate to mesothelioma? Not only are they new drugs they are in a new class of cancer treatments. Immunotherapy is a new class of therapies to treat certain types of cancer.

In order to understand the use of immunotherapy for cancers, such as mesothelioma, it is important to first understand the human immune system.

The Immune System

As researchers make progress toward treating cancer one system in the body plays an integral part in targeting new therapies. The immune system is a sophisticated, complex, system that functions to prevent or limit infections. It can be confusing and overwhelming when your Doctor starts talking about possible treatments that involve the immune system. We also hear and see ads that talk about boosting our immune system with certain products and supplements. What does it all mean? What should you be doing or not doing? Does a certain lifestyle contribute to making you more susceptible to a compromised immune system? How does the immune system work every day to help us stay healthy? What causes the immune system to turn bad on us- develop diseases such as “auto immune diseases’? Is the future to treating and controlling cancer in targeting the immune system?

Let’s start with a definition of what the immune system is. According to www.Merriam-Webster.com: Medical Definition of immune system

  • : the bodily system that protects the body from foreign substances, cells, and tissues by producing the immune response and that includes especially the thymus, spleen, lymph nodes, special deposits of lymphoid tissue (as in the gastrointestinal tract and bone marrow), lymphocytes including the B cells and T cells, and antibodies

The immune system is not located in one place, like your lungs, but it is a collection of organs, special cells, and substances that act to protect the body from infections. It is located in skin, bone marrow, blood stream, thymus, lymphatic system, spleen, mucosal tissue of the G.I. tract.

The cells start in the bone marrow and develop into mature cells through a series of changes that occur in different areas of the body. The largest organ of the body, our skin, is the first line of defense against potential harmful bacteria. Skin cells produce and secrete antimicrobial proteins, immune cells, which can be found in specific layers of skin.

Bone marrow is located deep inside our bones. Stem cells are found there, they can develop into a variety of cell types. “The common myeloid progenitor stem cell in the bone marrow is the precursor to innate immune cells- neutrophils, eosinophils, basophils, mast cells, monocytes, dendritic cells, and macrophages- important first-line responders to infection.” www.niaid.nih.gov/topics/immuneSystem

Lymphocytes are a type of white blood cells that are very important to the entire immune system. The lymphocyte determine how and what the response will be to infectious organisms and other foreign substances.

Lymphocytes may have immunological memory and also can mount an immediate defense. Natural killer (NK) cells share features of both innate and adaptive immune cells. Lymphocytes are B, T, and NK cells. B cells and T cells are adaptive immune cells. They have a memory- immunological memory- they respond to previous encounters they have had with microbes.

The blood stream has immune cells circulating throughout it. A reflection of how the body is in balance is when a complete blood count (CBC) is drawn. The lab is able to give a white blood count (WBC) and other cell counts to indicate if there is a problem. In adults lymphocytes make up approximately 20 to 40 per cent of the total number of white blood cells.

The thymus is located in the chest, behind the sternum and between your lungs. It has two lobes and reaches a maximum weight of I ounce, around puberty. After puberty it shrinks and turns into a fat deposit. The thymus is important in the production and maturation of T cells. T cells are a specific type of white cells.   All T cells are produced by the time of puberty. The thymus is responsible for secreting a hormone, thymosin, necessary for T cell development and production. From the thymus the T cells migrate to the lymph nodes, throughout the body. Hodgkin disease and non-Hodgkin lymphomas, are examples of lymphocytes that have gone bad and develop into cancers.

Lymph is a fluid outside the cell- extracellular – that helps connect the lymphatic system with lymphoid organs, such as lymph nodes. The lymphatic system is how communication happens between tissues and the blood stream. Lymph nodes are where immune cells converge, lymph nodes are throughout the body. Lymph nodes become swollen when a foreign substance invades the body and the cells then activate, replicate, and leave the lymph node to find the pathogen.

The spleen is an organ located under the rib cage in the upper far left of the abdomen, left of the stomach. It is on average about 4 inches long. The spleen functions as a filter for blood. Old red cells are recycled in the spleen, platelets and white cells are stored there.

Mucosal associated lymphoid tissue (MALT) is found along the mucosal lining of the respiratory tract and the G.I. tract. Mucosal surfaces are where pathogens can gain entrance. It also is recognized as the most extensive component of lymphoid tissue. Examples of these tissues are the tonsils, peyers patches within the small intestine, and the veriform appendix.

What is Cancer Immunotherapy?

Immunotherapy is an exciting new class of treatments for specific cancers. The immune system is a complex system of the body, involving many moving parts. The immune system functions to protect us from foreign substances that might produce infections, diseases, and upset the steady state of our bodies. It is known that the cells of the immune system have specific tasks that they perform.   Some of the components of the immune system are the dendritic cells, B cells, cytokines, regulatory T cells, CD4+Helper T Cells, CD8+ Killer T Cells, antibodies. All have specific functions. For example CD8 + Killer T Cells function to kill harmful cells such as cancer cells. They can seek out and kill the cells, such as viruses and proteins that are expressed by the cancer cells. A way to help fight cancer is to target those cells to kill the cancer cells, and enhancing them to eliminate the cancer and sustain the therapy, leading to a cure.

How does Cancer Immunotherapy work?

The way the treatments work is to use the immune system in a few targeted ways. The drugs are designed to take the way the immune system works for the good and enhance that. The first way is to stimulate your own immune system to work harder to attack cancer cells. The second way is to give your immune system components, such as man-made immune system proteins to help fight cancer. Some researchers are predicting that immunotherapy will be the way of the future in treatment of certain cancers.

Immunotherapy for Mesothelioma

Overall, immunotherapy is targeted to be very specific and precise. It is targeted for specific proteins expressed by certain types of tumor cells. In mesothelioma it is known that the cancer expresses certain proteins. When using the drug Pembrolizumab, in a clinical trial of patients with mesothelioma, Pembrolizumab, a monoclonal antibody, is used to block a protein called programmed cell death 1 (PD-1). It is theorized that it will then stimulate an immune response and kill tumor cells. This particular immunotherapy is given intravenously at 2-3 week intervals.

With the complexity of the immune system, scientists are very excited that they are seeing positive results from this new class of treatments for cancer. Mesothelioma is a complex tumor and breaking it down with this entire new treatment option, has given hope to a cure.

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Your message to us will be held in strict confidence. All requests for information by mesothelioma patients and their family members will be answered within 24 hours. Mesothelioma Treatment and Care Guides are sent to mesothelioma patients and families by overnight delivery.

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