Cancer Immunotherapy for Dogs

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Cancer Immunotherapy for Dogs

In my article about allergen-specific immunotherapies, I talked whereby the goal is for the body to reach a higher level of tolerance to an offending environmental agent such as pollen.

On the other side, cancer immunotherapies are more about destroying. Immuno-oncology research has focused around training the body to find and fight cancer cells or breaking its tolerance to those cells. This is one of the most exciting areas of research today and is growing rapidly. Although, when science reaches breakthroughs quickly, confusion and
misunderstanding can occur, because of:  

  1. Use of the word, “vaccine”. Traditionally, when we think of vaccines, we think of preventing infectious diseases from viruses or bacteria they even have the chance to begin. Recently, vaccines have been used to treat or blunt existing disease. The principle – introducing a substance to elicit an immune response to fight off infection or disease – is
    the same.
  2. The fact that not all immunotherapies are vaccines. Some other cancer immunotherapy treatment options are use of:
    a. Monoclonal antibodies: Man-made versions of the immune system proteins. Antibodies designed to attack a very specific part (clone) of a cancer cell.
    b. Immune checkpoint inhibitors: Drugs that take the “brakes” off the immune system, which helps it recognize and attack cancer cells.
    c. Non-specific immunotherapies: These treatments boost the immune system in a general way, which can still help the immune system attack cancer cells.

Let’s look at a few examples that are available today.

Prevention

We’ve been hearing a lot these days about the sexually transmitted Human Papilloma Virus (HPV) and the vaccine to prevent HPV infection. You may remember HPV from high school health class as genital warts, thanks to the vivid images presented. What you may have forgotten is the bit about HPV causing cancer later on in life. Nowadays, you may think, “Oh, I don’t have HPV because I never had warts so I don’t have to worry about cervical cancer.” Wrong.

The strains causing genital warts are different than those causing cancer. In fact, over 100 strains of HPV exist, but approximately 40 can infect the genital areas of males and females to cause cancer or warts. Meaning: not all strains perpetuate cancer or warts. Plus, most people do not know they are infected with HPV because they never develop symptoms or health problems. Most HPV infections (9 out of 10) go away by themselves within two years.  

The latest HPV vaccine available, Gardasil-9, is formulated to prevent infection from nine different strains of the virus that can cause cancer or genital warts. Granted, HPV is not the only thing to cause cancer, but it is the number one cause of cervical cancer.

More about HPV Vaccines

Current human HPV vaccines contain more potent aluminum nanoparticle adjuvants [Adjuvants are added to vaccines to: accelerate, prolong, and enhance antigen-specific immune responses; but they are just as likely to cause adverse vaccine-associated events (AE) as the antigens.]

Since 2009, HPV vaccines have been linked to 152 cases of serious AE, 129 (85%) were neuro-ophthalmologic disorders. Both adjuvants and dietary aluminum are known to accumulate in the central nervous system resulting in Alzheimer’s like symptoms, and even psychiatric disorders. Clinical trials for HPV vaccine used aluminum-containing placebo, thus potentially obscuring vaccine safety issues with the known neurotoxic aluminum placebo. An equal number of AE were found with both the vaccine and placebo cohorts; but there was a 50% reduction in cervical cancer after use of the vaccine.  So, this vaccine poses a benefit vs risk dilemma.

Other regional cancers are also linked with HPV:

  • Vulvar cancer: 69% of cases are linked to HPV.
  • Vaginal cancer: 75%
  • Penile cancer: 63%
  • Anal cancer: 91%
  • Cancer of the back of the throat: 72%

Cancer Treatment Vaccines

Malignant melanoma is a form of skin cancer in humans and dogs that affects the cells, called melanocytes, that are responsible for producing melanin. In dogs, these melanomas typically originate as tumors in the mouth but can also be found on the skin, nailbed, eye or footpad. It is a fast-spreading cancer that can infect the liver, kidneys, lungs or lymph nodes.

Once the cancer is diagnosed and the tumors are removed, veterinary oncologists can prescribe the vaccine, Oncept. Oncept is a weakened dose of tyrosinase, an enzyme located in the melanocytes that initiates melanin production and converts the protein, tyrosine, to dopaquinone. However, we are not giving dogs canine tyrosinase, but rather human DNA for the tyrosinase gene. Human tyrosinase is 85% identical to canine tyrosinase to enable it to elicit the reaction we want but not harm the dog.

Once the vaccine is introduced, the dog’s body should start to produce the human protein. The body recognizes it as a “foreign” invader, and so should start to attack and kill it. This attack breaks self-tolerance so that immunity should be achieved.

Survival data six months after Oncept use demonstrated that less than 50% of treated dogs died of disease related to canine oral melanoma. Additional research has also demonstrated that Oncept increased the life expectancy of those that did pass away from canine oral melanoma. While it is not perfect, results are very encouraging.

Monoclonal Antibodies

Monoclonal antibodies are manufactured to attach to specific protein clones on cancer cells. Approximately three different ways have been developed that use these antibodies. Their use really depends on the type of cancer one might have. They:

  1. Signal the immune system to attack and kill cancer cells. The monoclonal antibodies bind to the cancer cell and then tell the immune cells to “punch holes” in the cancer cell.
  2. Attach to the protein that blocks the cell receptor from receiving the message to either divide or grow.
  3. Carry radiation or cytotoxic drugs to the protein and kill the cancer cell.

Most research and development using monoclonal antibodies has focused on human medicine. In 2014, Josef Singer and Judit Fazekas of the University of Vienna developed formulae that needs more study but thus far work well for dogs.

W. Jean Dodds, DVM
Hemopet / NutriScan
11561 Salinaz Avenue
Garden Grove, CA 92843

References

Grosenbaugh, Deborah A., DVM et al. “Safety and Efficacy of a Xenogeneic DNA Vaccine Encoding for Human Tyrosinase as Adjunctive Treatment for Oral Malignant Melanoma in Dogs following Surgical Excision of the Primary Tumor.” American Journal of Veterinary Research 72.12 (2011): 1631-638. American Veterinary Medical Association Journals. Web. 18 Dec. 2016. http://avmajournals.avma.org/doi/abs/10.2460/ajvr.72.12.1631?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed.

Inbar, R et al. “Behavioral Abnormalities in Female Mice following Administration of Aluminum Adjuvants and the Human Papillomavirus (HPV) Vaccine Gardisil.” Immunological Research (2016): 1-14. Springer Link, 16 July
2016. Web. 18 Dec. 2016. http://link.springer.com/article/10.1007%2Fs12026-016-8826-6.

Singer, Josef et al. “Generation of a Canine Anti-EGFR (ErbB-1) Antibody for Passive Immunotherapy in Dog Cancer Patients.” Molecular Cancer Therapies 13.7 (2014): 1777-790. American Association for Cancer Research. Web. 18 Dec. 2016. http://mct.aacrjournals.org/content/13/7/1777.

“The Link Between HPV and Cancer.” Centers for Disease Control and Prevention, 30 Sept. 2015. Web. 18 Dec. 2016. http://www.cdc.gov/hpv/parents/cancer.html.

“What Is Cancer Immunotherapy?” Cancer.org, n.d. Web. 18 Dec. 2016. http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/immunotherapy/immunotherapy-what-is-immunotherapy.

 

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