How cellular immunotherapy is making a difference in veterinary oncology
Despite all the advancements in human medicine over the past few decades, veterinary medicine has seen little change until recently. Now, several new therapeutic developments have emerged specifically for use in veterinary medicine that have promising potential in changing how veterinarians treat cancer.
This article is sponsored by Elias Animal Health.
Cancer is a devastating disease for humans and the pets who are integral parts of their families. Cancer arises through accumulation of thousands of mutations, some of which generate drivers that lead to malignant transformation and cancer spread. Some of those mutations generate proteins that are recognized as foreign by the cancer-bearer’s immune system (cancer neoantigens). The growth and spread (metastasis) of a cancer involves complex interactions between cancer cells and normal host cells that populate the cancer tissue microenvironment. Some of those host cells suppress naturally occurring immune responses, which further promotes cancer growth and spread.
Recent advances in the fourth pillar of cancer treatment—immunotherapy—suggest that the immune system may be our best tool to cure more cancers. Various immune stimuli, including cancer vaccines and other biological response modifiers have been tested in dogs and humans with variable degrees of success. However, a notable challenge with these therapies is that while they will generate powerful immune responses against cancers, the effects of the immune cells—specifically T cells—that are generated from the stimulation and that infiltrate cancer tissue can be significantly suppressed by the cancer microenvironment. An example of these cancer defenses are checkpoint proteins on the surface of cancer cells. These checkpoint proteins identify cancer cells as “normal” cells and thus the immune system ignores them.
The capability of the immune system to kill cancer cells can be significantly boosted by removing T cells from the patient and converting them into effector T cells ex vivo, away from the immunosuppressive environment that exists within the patient’s body. One such approach that has had success in the treatment of leukemias and lymphomas is cellular immunotherapy with genetically engineered effector T cells called chimeric antigen receptor (CAR) T cells. Another that also has had considerable success in selected cancers is tumor infiltrating lymphocyte (TIL) therapy. Both CAR-T cell and TIL therapies have produced instances of cancer regressions and long-term patient survival when used to treat human patients with widespread metastatic disease.
ELIAS Animal Health is on the forefront of cancer immunotherapy research and development. The company is developing a unique new approach to the treatment of canine cancer that takes advantage of the fact that vaccinating a cancer-bearing individual with their own cancer cells can generate a significant immune response to the targeted cancer cells and ex vivo expansion and activation of a patient’s T cells can boost that immune response to produce more durable responses.
ELIAS’ adoptive cell therapy is being evaluated for the treatment of canine osteosarcoma. Data from the initial osteosarcoma study (n=14) demonstrated a favorable safety profile and showed 36% survivors at two years (JVIM, July 2020). Based on the promising results in that early study, the company has completed enrollment in a larger 1:1 randomized clinical trial evaluating its adoptive cell therapy in comparison to a four-dose carboplatin treatment regimen, current standard of care for canine osteosarcoma. Results of that pivotal study are expected in late 2022.
The immune system is complex and not all patients respond to a particular treatment the same way. Many scientists and medical professionals believe that better and more consistent patient outcomes will be achieved with therapeutic combinations. Given the myriad of defenses within the cancer microenvironment, it is not surprising that better outcomes for some patients have been achieved using multimodal combination therapies. ELIAS is actively pursuing innovative technologies that, when combined, will deliver safe and effective treatments to a broad population of patients.
New technologies referred to as checkpoint inhibitors disrupt the immunosuppression that can be created by cancers and reveal the cancer cells to the immune system. Checkpoint inhibitors are designed to alter the tumor microenvironment such that the immune system can cause cancers to regress and in responsive patients, survival can be greatly extended.
Oncolytic viruses are another emerging immuno-oncology modality and have exciting potential to improve outcomes by turning cold tumors ‘hot’. Oncolytic viruses cause cancer cell apoptosis which releases the cancer neoantigens, stimulates an innate immune response, alters the tumor microenvironment and generates a tumor-specific adaptive T cell response.
It’s a new day in veterinary medicine.
These exciting scientific advances may be the key to unlocking the possibility for better outcomes in pets with cancer. As new innovations continue to accelerate, ELIAS Animal Health is a pioneer in the endeavor to bring more of these treatment options to the veterinary market.