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Curing Cancer, Is Gene Therapy the Holy Grail?

Introduction


We are constantly bombarded by TV documentaries and reports that suggest a variety of both novel and less novel methods the healthcare industry is working on to finally solve the cancer conundrum. For those who watch Dr Michael Mosley’s (Trust Me, I’m A Doctor) TV series will understand the various therapies not only for Cancer but for a series of infirmities that appear promising at first sight. So, should we be getting excited? The answer is Yes. For the first time we are seeing great strides being made in a series of modalities that are showing promising results.


Cancer is a difficult disease to manage as it manifests in a variety of forms and is stubbornly difficult to fight. It is fair to say that over the past 10 years we have seen progress in certain cancer therapies without which would have had devastating outcomes to patients. Drugs have been developed to extend the life expectancies for patients who are unfortunately diagnosed with cancer. However, there has been momentum in finding therapies that look to eradicate the cancer totally. The current mode of therapy can include a combination of Surgery, Radiation, Chemotherapy and Immunotherapy. New research has led to discoveries that have the potential to attack cancer at the root, i.e. the mutated genes or even modifying genes as to destroy the cancer. Welcome to CAR- T therapy or even CRISPR (more on that in a later post) the latest in gene therapy.


What is Cancer?


Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells. If the spread is not controlled, it can result in death. Although the reason why the disease develops remains unknown for many cancers, particularly those that occur during childhood, there are many known cancer causes, including lifestyle factors, predisposition factors, such as inherited genetic mutations, hormones, and immune conditions. These risk factors may act simultaneously or in sequence to initiate and/or promote cancer growth.


According to the American Cancer Society, Lung Cancer is the biggest killer of cancer. See table below for the major cancer types.



Treatment


The types of treatment that one receives depends on the type of cancer and how advanced it is. Some patients with cancer will have only one treatment but most people have a combination of treatments. In addition to traditional treatments, the healthcare industry has been working zealously on Targeted Therapies that have higher efficacy rates and better outcomes in preventing the cancer from growing and spreading. Targeted therapy works by targeting specific genes or proteins. These genes and proteins are found in cancer cells or in cells related to cancer growth, like blood vessel cells. So, in effect attempting to suffocate or destroy the cancer from within.


Treatment types:

  • Surgery- The age-old method

  • Radiation Therapy – Intense on the body

  • Chemotherapy – Body takes a pounding

  • Immunotherapy – Strengthens the immune systems to fight cancer cells

  • Hormone Therapy – Changes hormone levels to treat breast and prostate cancers which rely on hormones levels

  • Stem Cell Transplant – Mainly used in blood cancers and for recovery after radiation

  • Targeted Therapy – Targeting the cancer cells to be recognised by the immune system or to interfere with signals the cancer needs to grow


Breakthrough Treatment


Targeted therapies are currently the focus of much anticancer drug development. They are a cornerstone of precision medicine, a form of medicine that uses information about a person’s genes and proteins to prevent, diagnose and treat disease. Recently, a highly personalised cancer treatment based on gene therapy known as CAR T-cell therapy (Chimeric Antigen Receptor T Cells) has shown positive results. Researchers began modifying T cells (part of the immune system) for patients in the 1990s and now CAR T-cell therapy is finally ready for treating cancer.


With all types of therapy there are side effects and risks, if the treatment is well tolerated and the benefits outweigh the risks the regulators tend to approve them.


What is Gene Therapy?


Human gene therapy is the administration of genetic material to modify or manipulate the expression of a gene product or to alter the biological properties of living cells for therapeutic use.


Gene therapy is a technique that modifies a person’s genes to treat or cure disease. Gene therapies can work by several mechanisms:

  • Replacing a disease-causing gene with a healthy copy of the gene

  • Inactivating a disease-causing gene that is not functioning properly

  • Introducing a new or modified gene into the body to help treat a disease


Risks


Like with many drugs that come to the market, drug producers tend to improve them for efficacy or to reduce the risk factors. CAR T therapies on the market have remarkable remission rates, 83% for Kymriah for B-cell acute lymphoblastic leukemia and 72% for Yescarta for Large B-cell Lymphoma. However, the side effects have been recorded to be severe with neurotoxicity and cytokine release syndrome. Drug companies are working hard to reduce these side effects with much-improved outcomes for patients.


How CAR-T Cell Therapy works


The therapy is made from a person’s own immune system.

  1. To start, a doctor removes blood where some white blood cells including T Cells

  2. The gene of the CAR is inserted into the T Cells and grown in a lab

  3. Those reprogrammed cells are sent back and administered to the patient to kill the cancer


Thus, CAR T-cell therapy turns the body’s own immune systems against cancer with genetic engineering. The first CAR-T drug called Kymriah, has shown good results for young patients with Acute Lymphoblastic Leukemia (ALL).


ALL is a cancer of the bone marrow and blood, in which the body makes abnormal lymphocytes (type of white blood cells). The disease


Current Gene Therapies


Drugs being investigated currently have different routes of applications and thus brings their own complexities, however, with the research being undertaken there is plenty of hope. So far, early stage clinical results have been encouraging not only for cancer but for a variety of diseases.


To date, there have been several drugs that utilise gene therapy to either treat or eradicate diseases, which is quite remarkable given where we were only a decade ago.


Wenlock Global Fund’s Exposure


The fund currently has exposure to CAR T therapies with its holding in Celgene via its collaboration and subsequent pending acquisition of Juno Therapeutics. Celgene is the leader in blood cancer treatments with revenues of over $13bn in 2017. Recently, Celgene has disappointed in its pipeline products, however its deep line up of novel drugs to be approved over the next few years provides for better long term returns. 

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