The role of immunotherapy in veterinary practice

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The role of immunotherapy in veterinary practice

Immunotherapy offers a new approach to cancer, and involves re-educating the patient’s immune system to combat the disease

Cancer is a devastating disease resulting from mutations that lead to uncontrolled cell growth, which also changes the local microenvironment. Cancer is not only mutated cells, but also a complex tissue composed of cancer cells with an underlying matrix, all promoting tumor growth and metastasis. Immunotherapy offers a new approach to cancer, and involves re-educating the patient’s immune system to combat the disease. Immunostimulation against specific tumor-associated antigens (TAAs) can result in tumor and metastatic disease destruction. Because tumors are complex tissues, an immune response to a wide array of tumor-specific antigenic targets increases the odds of destroying a tumor.

Torigen is a team of veterinarians and cancer researchers who are building a research company that is able to evaluate emerging therapies for humans and adapt them for veterinary medicine. The company’s first product is a whole-cell tissue vaccine — a personalized cancer immunotherapy created from a patient’s resected tumor that has been used in over 600 veterinary cancer patients. The vaccine includes an enormous menu of patient-specific antigen targets. This article reviews Torigen’s autologous approach and product development of monoclonal antibody and targeted neoantigen vaccine strategies.

Whole-cell tissue vaccines

The goal at Torigen is to make personalized cancer immunotherapy accessible to veterinary patients. Our whole-cell tissue vaccine is considered by the USDA Center of Veterinary Biologics to be an experimental product until conditional or full licensure is approved. However, it is available now for use under the supervision and prescription of a licensed veterinarian.

The vaccine is custom-produced using patient tumor material (~5 g). The whole-cell tissue vaccine results in immune presentation of a vast menu of antigenic targets such as those offered by neoplastic cells, tumor extracellular matrix, and tumor-associated fibroblasts. Each of these latter components helps promote tumor growth, metastasis and immuno-tolerance, and can be directly targeted by the immune system when a patient is treated with a tissue-based vaccine. The more tumor-associated antigens presented, the greater likelihood of a successful immune response. The initial research on this approach was conducted in rodent models using prostate, ovarian and melanoma tumors.

This response was further improved by the addition of a novel adjuvant designed to enhance the cellular immune response. This adjuvant, Matrix Immune Modulator (MIM), consists of “sticky” proteins that allow antigens to bind and be processed by macrophages, promoting an anti-cancer immune response.

The combination of tumor tissue with MIM leads to increased concentrations of specific cytokines that stimulate cytotoxic CD8+ T cells – cells which lead to a directed immune-mediated anticancer response.

Sources: “Prevention of denovo prostate cancer by immunivation with tumor-derived vaccines”. MA Suckow et al. Cancer Immunology, Immunotherapy 2007. 56(8)1275-1283. “Prevention of human PC-346C prostate cancer growth in mice by a xenogenic tissue vaccine”. MA Suckow et al. Cancer Immunology, Immunotherapy, 2007. 56(8) 1275-1283. “Inhibition of prostate cancer by administration of a tissue vaccine”. MA Suckow et al. Clinical and Experimental Metastasis, 2008: 2005(8)913-918. “Use of an extracellular matrix material as a vaccine carrier and adjuvant”. MA Suckow et al. Anticancer Research, 2008: 28:2529-2534.

Veterinarians are invited to contact the Torigen team (which includes a cancer biologist, veterinarian oncologist and veterinarian surgeon) to discuss upcoming tumor removal cases, in order to better understand how to apply this technology to a specific case. A free tumor collection kit with a prepaid overnight express shipping label for tissue submission will be provided. To request a kit, visit torigen.com.

This photomicrograph shows MIM uptake by macrophages. DyLight 594-labeled MIM was exposed to THP-1 cells activated with PMA (to promote macrophage phenotype). After five hours of exposure to the labeled MIM, the cells were fixed.

The tissue collection process is simple. After tumor excision, a portion of unfixed tissue is submitted to the Torigen laboratory. It is important that the submitted tissue not be placed in formalin. Formalin strongly cross-links tumor-associated antigens, rendering them less effective in stimulating a targeted and specific response.

The product is returned to the veterinary practice in as few as three days from initial surgery — this is important since Torigen’s process “captures” currently-expressed TAAs, providing a contemporary immune stimulation without days or weeks of tumor cell culture or T cell expansion. Since tumors can mutate rapidly, we believe timely and specific immunostimulation is critical. The product is administered subcutaneously (1 mL) once weekly for three weeks.

The company can provide tumor-specific data on many tumor types based on a database of over 600 patients treated to date — contact 860-519-9956 or info@torigen.com for information.

Future directions

Torigen strives to be the leader in veterinary cancer immunotherapy. To succeed, the company is investigating ways to further improve vaccine approaches to cancer, for example:

  • Immune checkpoint inhibitors will further promote immune-mediated cancer attack. Specific monoclonal antibody therapies, PD-1, PD-L1 and CTLA-4, block the downregulation of T-cells within the tumor microenvironment. When the tumor is “inflamed” or has many T-cells, these therapies can ensure the T-cells remain active in the microenvironment and attack the tumor. The pairing of tissue vaccines with checkpoint inhibitors offers a novel way to fight cancer.
  • Another approach under investigation is the development of innovative neoantigen vaccines. While tissue vaccines offer a wide array of TAAs, Torigen will also create neoantigen vaccines based on identifying the important antigen targets specific to each patient’s tumor (neoantigens), and add additional doses of those neoantigens to the tissue vaccine as a way to magnify anti-tumor immunity. This requires technically-complex full genome and exome sequencing between tumor and normal tissue, and exploiting discovered differences to establish important neoantigens for inclusion in each patient’s vaccine.

Providing effective and affordable cancer immunotherapy to veterinary patients is the goal at Torigen. To that end, the company is committed to educating veterinarians about cancer immunotherapy and further emerging tools in cancer treatment. Our team of experts is available for a consult — contact us to learn more.

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