So what about immunotherapy?

The hot phrase in cancer treatment is immunotherapy right now. What does it mean for ALK+patients?  Sometimes, you hear that immunotherapy does not work? But why are we trying to fund and are funding vaccines? Don’t vaccines work with the immune system? This short summary is to clarify these questions for you.

There is an easy to understand website with a general overview of the immune system. https://kidshealth.org/en/parents/immune.html

In general, anything that helps your immune system to fight cancer is immunotherapy.  However, there are many parts of the immune system that scientists are using to help us fight cancer.  The following are various types of strategies currently being used. 

Immune checkpoint inhibitors, which are drugs that block immune checkpoints. These checkpoints are a normal part of the immune system and keep immune responses from being too strong. By blocking them, these drugs allow immune cells to respond more strongly to cancer. Medicines such as Keytruda (Pembrolizumab), Opdivo (Nivolumab), Tecentriq (Atezolizumab), Imfinzi (Durvalumab), Yervoy (Ipilimumab) are examples. The key checkpoint proteins are PD-Ldl-1, PDd-1, and/or CTLA-4 that are targeted mentioned
within this type of treatment. These treatments tend to be longer lasting and may have side effects that will linger on. However, for an ALK patients, our cancer is considered “cold” cancer. It is not very reactive to this type of therapy because there is usually minimal penetration of the immune system cells into the tumor. The immune system recognizes our tumor as mostly part of ourselves and is not prone to attack itself, making this strategy less likely to be effective.

Cellular therapy, which is a treatment that boosts the natural ability of your own T-cells or NK cells to fight cancer. In this treatment, immune cells are taken from your tumor or bloodstream. One type of treatment in this category that falls under this is called tumor-infiltrating lymphocyte therapy (TILs). Another subcategory for this type of therapy is called CAR-T therapy. A third subcategory is to use take Natural Killer (NK) cells and target your cancer. In all of these cases, those selected cells that are most active against your cancer are changed or sorted in the lab to better attack your cancer cells, grown in large batches, and put back into your body through a needle in a vein. There are members reporting that they are looking into this type of therapy. However, to date, no big celebrations.

Monoclonal antibodies are immune system proteins created in the lab that are designed to bind to specific targets on cancer cells. Some monoclonal antibodies mark cancer cells so that they will be better seen and destroyed by the immune system. Such monoclonal antibodies are a type of immunotherapy. Other monoclonal antibodies block proteins from interacting with each other, and/or keep proteins from functioning normally. Checkpoint inhbitors are in this category. Monoclonal antibodies are made using animals such as mice, a combination of mouse/human proteins, or fully human proteins. If it is mouse only, the antibody is named with -omab. If they are mixed mouse/human, the antibody will be named with an ending of -ximab and -zumab, depending on whether there’s more mouse vs. human portions. If it is fully human protein, then the name will end with a -umab. A common one that we may have heard about is Avastin (Bevacizumab). From the name, you can see it is a -zumab (mix of mouse/human protein). It targets VEGF, a protein that helps tumors grow new blood vessels. Monoclonal antibody treatments are usually intravenous injections or infusions. Our members often use Avastin to help with brain swelling/ brain metastasis control. It is a very effective treatment

Treatment vaccines work against cancer by boosting your immune system’s response to cancer cells. Treatment vaccines are different from the ones that help prevent disease. In the context of ALK, Dr. Awad/Dr. Chiarle’s vaccine is one of this type of vaccines. Treatment vaccines can be designed to help your immune system recognize your own personal tumor cells, or they can be designed to elicit an immune response to a particular type of cancer, such as our ALK+ tumors. Similarly, Dr. Lam’s vaccine is using this type of approach. It is training the immune system to recognize that ALK mutations are not part of the normal human genome, allowing the immune system to recognize mutations. A third method of treatment vaccine can be made from a type of immune cells called dendritic cells that can stimulate the immune system.

•      Immune system modulators enhance the body’s immune response against cancer. Some of these agents affect specific parts of the immune system, whereas others affect the immune system in a more general way. There are several of these drugs: thalidomide, lenalidomide, and pomalidomide.  This class of drugs works with interferon which enhances the activity of some white blood cells (NK cells & dendritic cells).  In addition, interferon may slow the growth of cancer cells or promote their death.  Interleukins, also called T-cell growth factors,  increase killer T-cells and natural killer (NK) cells. You may have heard of Erythropoietin which increases the production of red blood cells.  This medicine helps with chemotherapy-related side effects.  Normally, ALK patients do not use immune system modulators as a main treatment method; we use them in a supportive role.

https://www.cancer.gov/about-cancer/treatment/types/immunotherapy

https://www.webmd.com/cancer/immunotherapy-treatment-types

https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immune-checkpoint-inhibitors.html

https://www.genscript.com/immune-checkpoint-inhibitors.html

https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/immunotherapy/types/CAR-T-cell-therapy

https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/monoclonal-antibodies.html

https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/cancer-treatment-vaccines

https://www.cancer.gov/about-cancer/treatment/types/immunotherapy/immune-system-modulators

https://www.cbinsights.com/research/report/what-are-neoantigen-vaccines-personalized-cancer-treatment/

 Author: Alice Chou

With special thanks to Emily Venanzi for her contribution in this article.

Kirk Smith