What Is Immunotherapy?

One of the roles of the immune system is in part to recognize self and “foreign” proteins.  In the case of cancer, this implies recognition and elimination of cancer cells by the body.  There many challenges in developing effective immunotherapies including tolerance of the cancer cells to the therapy and destruction of the therapy by the immune system.

Cancer cells have may ways to avoid the immune system.  They can recruit myeloid-derived suppressor cells (MDSCs) into the tumor environment. The MDSCs suppress the local immune response to the cancer and promote invasion and metastasis via a variety of mechanisms.  Tumors can also increase numbers of Treg cells and this is often associated with a poor prognosis.  Cancer can produce many different kinds of cytokines which are proteins which can affect the growth/activity of immune system and blood cells.

There are several examples of immunotherapies including:

1. Bacillus Calmette-Guèrin (BCG) –  This is a live strain of a bacteria called Mycobacterium bovis that can be effective in treating transitional cell carcinoma in humans
2. Salmonella –  Salmonella is a type of bacteria that can be modified to to grow in tissues without the presence of oxygen. At the core of many tumors there is an area where the cancer cells can grow without oxygen; it is an area that is protected as many traditional therapies cannot penetrate these regions due to their lack of blood supply.  The intent of using the modified salmonella species to to inject them into the body were they can penetrate the core of the tumor, emit local toxins, and destroy the cells. One of the risks of this therapy is bacterial colonization of the patient.
3. Superantigens – Some types of bacteria produce toxins known as superantigens.  These toxins can stimulate the immune system and be toxic to the cancer cells, however they can elicit responses like toxic shock syndrome.
4. Liposome-Encapsulated Muramyl Tripeptide (L-MTP) –  This is a protein derived from bacterial cell walls that is encased in a protective layer (referred to as liposome encapsulation). These proteins can stimulate immune system cells and cytokines that can promote cancer cell death.  This therapy has been evaluated in dogs with osteosarcoma, hemangiosarcoma, and melanoma.  Some of the results suggest a better outcome with the L-MTP, but results are inconsistent and the product is not commercially available.
5. Cytokine therapy –  Cytokines can either promote cancer, or be used to treat cancer depending on the cytokine released.  Interferon is a classic example, but it can cause severe toxicity so use is limited.
6. Monoclonal antibodies(MAb) –  These are immune system proteins that are created in a lab to help the body recognize specific targets like cancer. As a general rule, the names of these therapies end in –mab.

Cancer vaccines are the ultimate goal of immunotherapy.  These vaccines can take weeks to months to result in a clinical response as opposed to more traditional therapies like chemotherapy or radiation.  There is only one cancer vaccine in veterinary medicine which is called Oncept.  Oncept is a vaccine that stimulates the [canine] immune system to produce a response and antibodies against tyrosinase. Tyrosinase is a protein in the body used in the synthesis of melanin and is present in many melanoma cancers.