IMMUNOTHERAPY BASICS

“If you can’t explain it simply, you don’t understand it well enough”.
This quote is often attributed to Einstein, but appears to have originated from someone else

WHAT IS CANCER

Cancer occurs when cells from a person’s own body grow when and where they shouldn’t. Many things can contribute to the development and progression of cancer, but an important principle is: most cancer cells contain multiple DNA mutations, which cause them to grow abnormally.

 

WHAT ARE THE WAYS TO TREAT CANCER

There are many different ways to treat cancer.  There are also many ways to categorize the various approaches.  This diagram shows some of the major categories, with focus on immunotherapy. Those in green highlight are approaches which we have expertise in.

WHAT IS IMMUNOTHERAPY

The term “immunotherapy” refers to the use of the body’s own immune system to fight disease. Immunotherapy is often used in reference to cancer, but immunotherapies are also being developed to treat other diseases, for example: allergies, multiple sclerosis and Crohn’s. Cancer immunotherapy is a term that encompasses a range of therapeutic approaches. These may include: antibodies, live viruses, vaccines and cell based techniques, among others.

WHEN DID SCIENTISTS FIRST BEGIN STUDYING IMMUNOTHERAPY AND WHY THE RECENT INCREASE IN INTEREST?

The concept of using the body’s own immune system to treat cancer has been around for a long time, arguably as early as 1891 when William Coley attempted to treat cancer patients by inoculating them with erysipelas. Since then many advances have been made, a very comprehensive timeline is available here. While several notable discoveries have been made in the field of immunotherapy over the years, it is really the collective efforts of scientists working across many disciplines that have made the current breakthroughs possible. Knowledge and equipment within the biological sciences and all scientific fields is constantly improving. For example, without the recent advances in DNA sequencing technology and the availability of powerful computers and software, we could not do many of the things that are taken for granted today. An example is the ability to sequence and analyze the human genome, this has been critical in our ability to understand and treat cancer.

The increasing interest in immunotherapy is being driven by encouraging data from clinical trials. Among the most important trials is one that was undertaken at the Seattle Children’s hospital in which 91% of patients with relapsed leukemia experienced complete remissions. The form of immunotherapy used in this trial is known as adoptive T cell transfer (the version using chimeric antigen receptors (CARs)) and this result demonstrated proof of principle for this approach in treating cancer. There is still work to be done to get immunotherapy to work as well for other cancer types, but this is happening now and breakthroughs will undoubtedly continue to take place. Now that working examples of immunotherapy are available, incremental improvements can take place, which should ultimately lead to very effective therapeutics. This is analogous in some ways to building the first airplane; The legend of Icarus illustrates how humans throughout the ages have wanted to fly, but the equipment and know-how were not available. Once the Wright brothers demonstrated a way in 1903, improvements were made very quickly. We are on the cusp of a new era in the Biomedical Sciences, cancer is curable and it’s starting to happen.

WHAT TYPES OF IMMUNOTHERAPY ARE WE MOST INTERESTED IN?

We are interested in using approaches with curative potential, that have the best chance of working and that can be profitable for our investor/s. There are many things to be considered and each approach has its own benefits and drawbacks. We have expertise in adoptive T cell transfer approaches (CARs and TCRs), vaccines and oncolytic viruses. These are very powerful approaches to fighting cancer which we believe will be among the most transformational in the coming years. However, all of the approaches have value and as new therapeutics pass through clinical trials, the most effective cancer treatment strategies will likely involve the use of a combination of several approaches.

WHAT ARE THE BENEFITS OF IMMUNOTHERAPY?

We believe that there are many benefits to immunotherapy for cancer and its use will continue to grow. Here’s why:

  • Immunotherapy works: Recent evidence from the clinics has demonstrated that these strategies can and do work.
  • Curative potential: Although immunotherapy is still in very early stages, there are already examples of complete remissions (cures) using a single immunotherapy approach.
  • Fewer side effects: Severe side effects are not an expected consequence of immunotherapy treatments, as they are for some other approaches.
  • Can be used in combination with other treatments: Low toxicities allow for the use of multiple therapeutic strategies in an individual’s treatment program
  • Few limitations on cancer type: Immunotherapy has the potential to work on virtually all cancers
  • Potential for personalization and predictable efficacy: Many immunotherapies are designed to target very specific genetic abnormalities that are present in some forms of cancer and not others. Genetic testing of a patient’s normal DNA and tumor DNA, will soon become routine and will be used to predict whether a particular therapeutic is likely to work or not.
  • Advances made in one form of cancer can be transferred to others: The nature of the way many immunotherapies work allows for advances made in one type of cancer to be applied to other types of cancer. This is a consequence of targeting specific genetic abnormalities.  CARs and TCRs can be used to illustrate this.  These therapeutics have a modular plug and play design, which allows much of the therapeutic molecule to stay constant regardless of the type of cancer being treated.  Only a small section of the therapeutic needs to be re-designed to make it target a different type of cancer.  This small cancer-specific section can be easily swapped out and replaced with a new one.  This allows for faster development of new therapeutics.
  • Advancements waiting to happen: Immunotherapy is still in early stages and many advancements can be made with relatively little effort. In the vernacular; the fruit is low-hanging.  Several of the most difficult challenges have been overcome and the ground work is now set for relatively rapid advancement of this technology into the clinics.
  • Potentially lower clinical trial failure rates: Though yet to be determined, it is possible that immunotherapies will have greater success rates in clinical trails. There are several reasons for this, mainly related to reduced variability and improved predictability because specific genetic abnormalities are targeted, rather than general cellular processes.  Furthermore, with some approaches, safety measures can be implemented which will shut off the therapeutic if it is having negative effects. Immunotherapies that do fail clinical trails may tend to fail earlier in the process, which is highly preferable.

Simply put, cancer immunotherapy makes sense. The immune system is already designed to attack and destroy cancer cells, it just needs a little help. There is still work to be done, but the various immunotherapy approaches provide the framework to do it.