Recently, a new treatment for human B cell cancers called CAR-T (Chimeric Antigen Receptor T cell) therapy has made headlines around the world, because the new immunotherapuetic treatment is showing great promise in producing durable remissions in patients with advanced disease.
The Food and Drug Administration first approved this new type of immunotherapeutic treatment for children and young adults with a recurrent form of a blood cancer called Acute Lymphoblastic Leukemia in August 2017. Since August, the FDA also approved this CAR – T cell approach to treat adults with B cell non – Hodgkin’s lymphoma (B – NHL). According to an article in Popular Science, “The FDA Just Approved A Game-Changing Cancer Treatment” by Claire Malderelli, in CAR-T therapy a patient’s own immune cells are genetically engineered in the laboratory to express a CAR that directs them towards a target molecule. Then the altered T – cells are infused back into the body where they seek out cancer cells that express the target molecule recognized by the CAR and eliminate them. Importantly, the genetically modified CAR-T cells can persist for long periods of time in the patient’s body where they provide on – going surveillance against cancer cells. This long term persistence and ability of these cells to re-activate and eliminate re – emerging cancer cells is thought to be responsible for the durable clinical remissions that are being seen in these patient populations.
Will CAR-T Therapy Help Pets?
Non – Hodgkin’s Lymphoma (NHL) is the most common cancer in dogs and the most common sub-type is Diffuse Large B – Cell Lymphoma (DLBCL). While combinations of chemotherapy agents lead to clinical remission in approximately 75% of dogs, most dogs relapse within six to nine months of standard treatment, a statistic that has remain unchanged for the past 30 years. An urgent need exists for new therapies for canine lymphoma. Furthermore, evaluation of these new therapies in pet dogs with naturally-occurring cancer may also provide important information to help advance novel therapies for people.
With support from Animal Cancer Foundation, Dr. Nicola Mason, Associate Professor of Medicine at the University of Pennsylvania’s School of Veterinary Medicine and Dr. Avery Posey, Clinical Instructor at the University of Pennsylvania’s School of Medicine, have developed CAR T cell therapy for use in the dog. Using advanced genetic engineering approaches, they have previously shown that canine CAR T cells, these genetically modified canine T cells can become activated, proliferate and kill upon encounter with target B cells.
Now, in a first-in-dog clinical trial currently ongoing at the University of Pennsylvania School of Veterinary Medicine, canine patients with relapsed, refractory B cell lymphoma or leukemia are being treated with CAR T cell therapy. Preliminary results are encouraging and the investigators are continuing to explore new ways to improve the persistence and function of these canine CAR T cells in dogs afflicted with DLBCL. Animal Cancer Foundation’s grant to Dr. Mason and Dr. Posey is allowing the team to identify the best canine CAR construct to achieve durable remissions in canine B cell lymphoma.
Current CAR T therapy in people is not without significant side effects. Longer term, veterinary oncologists hope to establish a promising immunotherapeutic platform that will enable assessment of novel CAR T agents and the next generation CAR design that will help to improve effectiveness and reduce side effects of CAR T treatment for both canine and human patients.
The investigative team is hopeful that personalized cell based therapies will become streamlined and that further investigations, including the current ACF funded research, will lead to increased safety and effectiveness of CAR T cells and more rapid product development so that this approach may be more widely accessible for pet patients.