Building on a listeria-based immunotherapy developed by Yvonne Paterson—then a microbiologist at the Perelman School of Medicine—that showed promise for the treatment of breast cancer in preclinical models, Mason and her team conducted a pilot study vaccinating dogs diagnosed with bone cancer after standard amputation and chemotherapy with this therapy. The therapeutic vaccine targeted HER2, a protein expressed in breast cancer and osteosarcoma, a devastating bone cancer common in dogs and, in rare cases, children. “We found that we could safely delay the onset of metastatic disease, and in some notable cases, prevent metastatic disease,” she says.

That trial laid the foundation for the Comparative Immunotherapy Program, which Mason, a professor of medicine and pathobiology in the School of Veterinary Medicine, established to tap into Penn’s deep expertise across schools and capture similar opportunities.

A collaborative, cross-disciplinary approach

Launched one year ago, the program is already enrolling canine patients in two adoptive cellular therapy clinical trials. The program fosters collaborative, cross-disciplinary innovation and accelerates clinical translation of immunotherapeutic approaches for canine and human patients with cancer, autoimmunity, infectious disease, and organ failure requiring transplant.

The goal, says Mason, is to “leverage a comparative approach to better understand the immunobiology of disease and accelerate the clinical translation of innovative immunotherapies into the human and veterinary clinic to improve health for humans and animals.”

At Penn, many researchers are developing immunotherapies—treatments that stimulate the immune system to fight diseases. Mason says translating those into the clinic can be challenging. “Pet dogs develop diseases spontaneously in the same way humans do. And many of those diseases, particularly cancer and autoimmunity, share biological, behavioral, and clinical features with the human disease; the similarities are quite remarkable,” she says. “We have faithful ‘models’ of human disease living with us and needing novel therapies to improve their clinical outcome.”

“We can use this parallel patient population to accelerate translation of therapeutic strategies into the clinic and to determine correlative biomarkers of response that can inform human clinical trials,” she adds. “Dogs benefit, and humans benefit.”

Expanding into cell therapies and other diseases

Mason’s team at Penn Vet has expanded into cell-based therapies like chimeric antigen receptor T (CAR T) cell therapy, which reprograms a patient’s immune cells—specifically T cells—to target cancer, building on the work of Jacob Svoboda and Carl June of the Perelman School of Medicine.

They are evaluating “armored” CAR T cells—anti-CD19 CAR T cells that secrete canine interleukin-18, a cytokine known to boost antitumor activity—to treat B cell lymphoma or leukemia. In collaboration with Penn Med’s Dan Powell, the team is administering these cells intratumorally and systemically to learn more about their effects on the tumor microenvironment. This trial is currently enrolling patients.

A second trial supported by the National Cancer Institute is evaluating genetically engineered invariant natural killer T (iNKT) cells expressing a CAR in dogs with metastatic osteosarcoma. Two patients have been enrolled.

“These are a very rare set of T cells that have very potent cytotoxic capabilities that can be transferred from a healthy donor to a patient without causing graft-versus-host disease,” says Mason. “This is a real step towards the development of an ‘off-the-shelf’ CAR therapy and aims to inform a future pediatric osteosarcoma trial.”

The team also works with the Comparative Pathology Core and Penn investigators to assess the feasibility and value of canine studies in accelerating new immunotherapeutic approaches, providing expertise from developing and using canine (and some feline) in vitro assays to clinical protocol design and trial execution.

For example, Mason says they are working with Leyuan Ma of Penn Medicine to test a novel integrin-targeting CAR in canine T cells against solid tumor cell lines before piloting it in dogs with metastatic melanoma.

Looking ahead

The program continues to grow. Continuing their collaborations with Aimee Payne at Columbia, the CIP team is investigating the use of CAR T cells to treat the autoimmune disease pemphigus, a group of severe skin disorders that occur spontaneously in dogs and humans.

They are also working with Children’s Hospital of Philadelphia to help develop tumor cell lines and organoids, “mini tumors” in a dish, for early drug sensitivity and immunotherapy testing.

The team is ready to collaborate with other Penn researchers to bring promising therapies to clinic, learning about and treating disease simultaneously.

“Bringing the incredible firepower of the Penn immunology community into the veterinary space promises to accelerate therapies and identify biomarkers of response that not only inform human trial design in a meaningful way but also can help our dogs at the same time. It’s exciting, it’s inspiring, it’s motivating, and it’s happening at Penn!”