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Immuno-Oncology

Immuno-Oncology


The job of our immune system is to act as a sentinel and to intercept any invading pathogens or abnormal cells within the body, including cancer cells. The immune system has evolved numerous mechanisms to recognize such threats all the while limiting the risk of autoimmunity or attack on normal cells and tissues.

But what happens when the immune system doesn’t recognize cells that can be dangerous to animal health, such as many cancers? Those cells bypass the body’s natural defense system, proliferate destructively, and eventually challenge the body’s ability to function. In many cancers, malignant progression is accompanied by profound immune suppression that interferes with an effective antitumor response and tumor elimination.

Over the past decades, physicians and researchers in both human and veterinary medicine have partnered to develop ways to reverse this immunosuppression or otherwise make the immune system recognize and attack cells that previously passed undetected. These types of treatment – immunotherapy and immuno-oncology – offer novel and exciting approaches to treating certain types of cancer.

Immunotherapy treatments can: 

  • Boost the body’s immune system in a general way, thereby encouraging a more aggressive environment towards fighting cancer cells.
  • Train the immune system to attack cancer cells specifically through the use of tumor vaccines or immune cell bioengineering, (e.g. CAR T-cell therapies).
  • Block the immunosuppressive properties of tumors and the associated tumor microenvironment allowing for the immune system to function properly and mount an anti-tumor response.

Penn Vet is a key site for conducting novel immunotherapies, and aggressively pursuing new ways for veterinary medicine to address canine and feline cancers. Current available treatments based on tumor type include:

Hemangiosarcoma

Hemangiosarcoma is a common, aggressive cancer that arises from the cells that line blood vessels. Common sites of occurrence include the spleen, liver, and the right side of the heart.

The current standard of care for hemangiosarcoma that occurs in the spleen is surgical removal of the spleen followed by chemotherapy. Unfortunately despite surgery and chemotherapy, the disease usually spreads and most dogs succumb to their disease within 6-12 months of diagnosis.

Anti-vascular Endothelial Growth Factor Therapy

Vascular endothelial growth factor (VEGF) is a growth factor that may contribute to the spread and growth of hemangiosarcoma. In this clinical trial, we will evaluate the safety and effectiveness of an antibody therapy designed to inhibit VEGF and delay or prevent spread of the disease after surgery.

  

Use of a Novel Immunotherapy for Dogs with Bone Cancer of the Leg

Osteosarcoma (OSA) is an aggressive cancer that frequently arises in the long bones of large-breed dogs. Approximately 90-95% of dogs with osteosarcoma have undetectable metastatic disease at presentation. Despite limb amputation and follow-up chemotherapy, most dogs are euthanized due to progressive metastatic disease within a year of diagnosis.

Dogs enrolled in this clinical trial will receive a HER2-targeting bacterial vaccine after amputation and chemotherapy. This immunotherapy has shown promising results in preventing metastatic disease when evaluated in a small number of dogs with osteosarcoma after surgery and chemotherapy.

Immunotherapy For Dogs With Transitional Cell Carcinoma

Transitional cell carcinoma (TCC) is the most common type of bladder cancer in dogs. Most dogs with TCC initially show signs such as straining to urinate, increased frequency of urination, or blood in the urine. As the tumor grows, it obstructs the flow of urine, which can become life-threatening. TCC can also spread to nearby lymph nodes, lungs, and bones. In most cases, TCC of the bladder cannot be cured.

Common treatment options include nonsteroidal anti-inflammatory drugs (NSAIDs), chemotherapy, stent placement, or radiation therapy. Most dogs with TCC of the bladder succumb to their cancer within 6 to 8 months of diagnosis.

Recently, a tumor protein called V600E B-Raf has been identified in up to 87% of dogs with TCC. This clinical trial is evaluating a bacterial vaccine that encourages the immune system to target the V600E B-Raf protein. We aim to determine if this vaccine is safe, and if it can delay tumor growth or spread and extend survival in dogs with TCC.

 

Antibody Therapy for Dogs with Splenic Hemangiosarcoma

Hemangiosarcoma is a common, aggressive cancer that arises from the cells that line blood vessels. Common sites of occurrence include the spleen, liver, and the right side of the heart.

The current standard of care for hemangiosarcoma that occurs in the spleen is surgical removal of the spleen followed by chemotherapy. Unfortunately despite surgery and chemotherapy, the disease usually spreads and most dogs succumb to their disease within 6-12 months of diagnosis.

Vascular endothelial growth factor (VEGF) is a growth factor that may contribute to the spread and growth of hemangiosarcoma. In this clinical trial, we will evaluate the safety and effectiveness of an antibody therapy designed to inhibit VEGF and delay or prevent spread of the disease after surgery.

 

ALVAC® IL-2 Treatment in Cats with Feline Fibrosarcoma

FSA is one of the most common cancers in cats. These tumors develop in the subcutaneous tissues and can invade extensively into the adjacent skin and muscle. Because of this, complete surgical removal can be difficult and recurrence of the tumor is common. Current standard of care treatments include various combinations of surgery, radiation, and chemotherapy.

ALVAC IL-2 is a type of immunotherapy. It is an injection designed to help a cat’s immune system to kill any cancer cells that remain following surgery.

Re-directed Autologous T cell Therapy for drug resistant or refractory CD20+ B cell malignancies

In this approach, immune cells (known as T cells) are taken from the peripheral blood, genetically modified in the laboratory to express a receptor that recognizes B cells, and then expanded to produce large numbers of tumor specific T cells outside of the body.

These genetically modified (re-directed) T cells are then infused back into the body where they will seek out B cells and kill them. This process is known as adoptive immunotherapy and the cells that are infused into the patients are known as chimeric antigen receptor T cells (CAR T cells).

The approach has shown promising results in people with blood cancers such as chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL).  

 

Clinical Advancement of RNA-transfected CD40-B Cell Vaccine Technology for Cancer Therapy

The purpose of this study was to determine whether repeat vaccinations with a cancer vaccine, made from your dog’s own immune cells (B cells), can prevent relapse of lymphoma when given following a standard 19-week course of chemotherapy. 

 

Penn Vet Expertise

At Penn Vet, we offer a unique combination of doctorate-level clinician-researchers, each of whom is board-certified in their clinical specialty, specializing in the basic, translational, and clinical approaches of immuno-oncology.

Immunotherapy/Immuno-Oncology Clinician-Researchers
Dr. Oliver Garden, Penn Vet
Dr. Nicola Mason, Canine Cancer Studies
  • Associate Professor, Medicine
  • Internal Medicine
  • Canine Cancer
  • Immunotherapy
Dr. James Perry, Penn Vet

 

Here are some additional resources on immunotherapy and immunobiology research taking place at Penn Vet: