Atherton Laboratory

Our research is focused on developing next-generation immune therapies adopting a One Health approach. The Atherton Lab utilizes patient samples from the veterinary and human clinic to inform a pipeline to bring our discoveries from the bench to the (dog)bedside. In collaboration with experts across the Penn Campus at both the Vet School and Penn Medicine we are driven to improve the health of our pets and their owners. Our current areas of interest include: 

1. Preclinical development of cutting-edge CAR T cells for canine cancer patients.

Penn Medicine has been at the forefront of developing lifesaving CAR T therapy for people diagnosed with B cell cancers. Studies at Penn Vet have revealed that CAR T cells are a safe approach for dogs diagnosed with B cell lymphoma with early signs of clinical activity. Observations during these trials provided the rationale for manufacturing next generation canine tandem CAR T cells and work is ongoing in the Atherton Lab to optimize these promising constructs prior to assessment in the veterinary clinic. We are concurrently designing CAR T cells capable of targeting sarcomas and other less frequently observed hematologic cancers to improve the outcomes of our own patients and help inform early-stage trials of rare cancer types in human patients.

2. Interrogating the immunologic tumor microenvironment (TME) of hematologic malignancies

Histiocytic sarcoma is a deadly cancer in dogs and people with limited treatment options. Our multi-species work revealed the importance of T cells in shaping the prognosis of patients diagnosed with histiocytic sarcoma using parallel multiplexed assays. This discovery lays the foundations for developing T cell therapies for patients of both species and research in the lab is continuing to define targets for T cell therapy and mediators of immune suppression that need to be overcome to enable successful immunologic interventions. The Atherton Lab is also actively investigating the immune TME of canine mast cell tumors and high-grade lymphomas to help dissect the interaction of the immune system with cancer cells in these diseases. 

3. A roadmap to establish adoptive cellular therapy in the veterinary clinic

In parallel to our preclinical research and development pipeline and investigations of the immune TME we are performing a first in dog clinical trial assessing the safety, activity, and immunomodulatory properties of bendamustine for high grade canine lymphoma. Pre-conditioning treatment with drugs including bendamustine have proven vital for the activity of CAR T cells in human trials thus we are working to characterize this drug in veterinary oncology. Ongoing collaborations with the Penn Medicine are underway to develop a customized toolbox of assays to monitor CAR T cell safety and activity in our veterinary patients. Collectively these projects will allow a smooth transition of our bespoke CAR T products into comprehensive clinical trials assessing their safety and activity.

Matt Atherton, BVSc, PhD (PI)
Assistant Professor of Immuno-Oncology

Dr. Matt Atherton completed veterinary school at the University of Bristol. Following three years in mixed practice Matt undertook a rotating internship at the Royal Veterinary College. Matt gained board certification in medical oncology following residency training at the University of Glasgow and was awarded Master of Veterinary Medicine for researching the serum proteome in canine lymphom. Subsequently he defended his PhD at McMaster University with data from this research enabling “first-in-man” oncolytic virotherapy trials for epithelial malignancies. Matt completed post-doctoral training at McMaster and the University of Pennsylvania where he studied novel approaches to cancer immunotherapy prior to starting a comparative oncology lab at Penn Vet in November 2022. The primary focus of the Atherton Lab is dissecting the interplay between the immune system and cancer with a goal of developing next generation adoptive T cell therapies for hematologic malignancies utilizing a One Health approach. As a clinician scientist Matt enjoys seeing general medical oncology clinics and is a member of the Comprehensive Care Team at the Ryan Veterinary Hospital where research generated in the lab is used to inform clinical trials for veterinary cancer patients.

Jenny Lenz, DVM (Oncology Faculty and Collaborator)

Since joining the Penn Vet team as faculty in 2018, Dr. Jenny Lenz has played an active role as a Medical Oncologist within the Comprehensive Cancer Care service and is responsible for the oversight and training of oncology residents, interns, and veterinary students. Jenny’s primary research interest is to characterize the immune landscape of the tumor microenvironment in companion animals and identify spontaneous cancer models for translational research. Dr. Lenz runs several ongoing clinical trials enrolling dogs with cancer to investigate the immune landscape of lymphoma and determine the safety and efficacy of novel immunotherapies. As an affiliate of the Atherton Lab, Dr. Lenz collaborates closely in developing novel therapeutic approaches for hematologic malignancies utilizing a One Health approach.

Brandon Peng, BA (Lab Manager)

Brandon Peng is the current lab manager of the Atherton Lab at Penn Vet. He attended Colgate University and graduated with a bachelor’s in molecular biology with a specific focus in Global Public Health. Before joining the lab, Brandon investigated the role of the protein UGCG, that conferred resistance to autophagy inhibition in melanoma in the Amaravadi Lab at Penn Medicine. Brandon recently became invested in CAR T therapy and Brandon is now working on building a pipeline to efficiently design and manufacture tandem CAR T cells for the treatment of canine lymphoma, as well as developing functional
assays to assess their clinical function. Brandon is also interested in how the tumor microenvironment impacts canine T cell function. Outside of lab Brandon enjoys hiking, rock climbing, and exploring Philly with friends.

Dillon Didehvar, VMD (Oncology Resident)

Dr. Didehvar grew up in Delaware, attended Virginia Tech for his undergraduate studies, and obtained his veterinary degree from PennVet. Dillon then completed a one-year general medicine and surgery rotating internship at the Animal Medical Center (AMC) in New York City. Returning to home base, Dillon undertook a one- year speciality internship in oncology clinical trials at PennVet before transitioning to his role as a resident in Medical Oncolgy. Dr. Didehvar is particularly interested in lymphoma/leukemia, comfort care, and quality of life. Dillon’s research project aims to immune biomarkers in canine lymphoma present at the time of diagnosis and disease relapse, to serve as early prognostic indicators for patients being treated with standard of care chemotherapy.

Katie Bardales, DVM (Oncology Resident)

Dr. Katie Bardales received her DVM from Midwestern University in 2018. From there, Katie completed a small animal rotating internship at Veterinary Referral Associates in 2019 and an oncology specialty internship at Washington State University in 2020. In 2021, Dr. Bardales joined the team at PennVet as a Medical Oncology resident. As part of residency training, Katie conducting a project in the Atherton Lab using transcriptional approaches to better elucidate the immune tumor microenvironment of cutaneous canine mast cell tumors. Our hope is to be able to identify biomarkers that can further help guide therapeutic recommendations and provide prognostic information for our patients.

Laurel Upton, DVM (Oncology Resident)

Dr. Laurel Upton grew up in New Orleans, Louisiana and went to Louisiana State University for both undergraduate and veterinary school. She completed a one-year general medicine and surgery rotating internship at MedVet New Orleans, a one-year specialty internship in medical oncology at Blue Pearl Nashville, and a one-year specialty internship in radiation oncology at Penn Vet prior to beginning her Medical Oncology residency at Penn Vet in July 2023. Laurel's research project aims to evaluate the activity of bendamustine chemotherapy on different canine lymphoid cell lines in vitro. This study will complement an ongoing clinical trial assessing the safety, efficacy, and immunomodulatory profile of bendamustine in canine lymphoma patients.

Evaluation of Bendamustine as a Novel Chemotherapy Agent for Relapsed Canine Lymphoma 

Bendamustine is a chemotherapy drug that is used to treat various types of cancer in people, including lymphoma, but it has not yet been evaluated in dogs with cancer. The purpose of this study is to evaluate different doses of bendamustine in dogs with lymphoma to evaluate its safety and effectiveness. Dogs may be eligible for this trial after relapsing from a standard chemotherapy protocol for lymphoma. Dogs will be actively enrolled in the trial for 21 days, consisting of 5 study visits and 2 doses of bendamustine. All standard of care tests and procedures and all study-related procedures performed during study visits 1 through 5 will be paid for by the study. 

For more information, please call the study coordinator at 215-573-6610 or email vcic@vet.upenn.edu.

https://www.inquirer.com/health/pets/canine-cancer-research-fund-penn-vet-miso-harris-20230719.html 

July 5th 2023 Brandon Peng Joins the Atherton Lab- welcome Brandon! 

2020-current: 

Panjwani M.K.*, Atherton M.J.*, MaloneyHuss M.A., Haran K.P., Xiong A., Gupta M., Kulikovsaya I., Lacey S.F. & Mason N.J. Establishing a model system for evaluating CAR T cell therapy using dogs with spontaneous diffuse large B cell lymphoma. OncoImmunology. January 2020. *Contributed equally. 

Pol J.G., Atherton M.J., Stephenson K.B., Bridle B.W., Workenhe S.T., Kazdhan N., Mcgray A.J.R., Wan Y., Kroemer G. & Lichty B.D. Enhanced immunotherapeutic profile of oncolytic virus-based cancer vaccination using cyclophosphamide pre-conditioning. Journal for ImmunoTherapy of Cancer. July 2020. 

Atherton M.J., Lenz J.A. & Mason N.M. Sarcomas- a barren immunological wasteland or field of opportunity for immunotherapy? Veterinary and Comparative Oncology. December 2020. 

LeBlanc A., Atherton M.J., Bentley R.T., Boudreau E., Burton J., Curran K., Dow S., Giuffrida M., Kellihan H., Mason N., Oblak, M., Selmic L., Selting K., Singh A., Tjostheim S., Vail D., Weishaar K., Berger E., Rossmeisl Jr. J. & Mazcko C. Veterinary Cooperative Oncology Group – Common Terminology Criteria for Adverse Events (VCOG-CTCAE v2) Following Investigational Therapy in Dogs and Cats. Veterinary and Comparative Oncology. June 2021. 

Benjamin S.E., Sorenmo K.U., Krick E.L., Salah P., Walsh K.A., Weinstein N.M., Keuler N.S., Avery A.C., Atherton M.J. & Lenz J.A. Response-based modification of CHOP chemotherapy for canine B-cell lymphoma. Veterinary and Comparative Oncology. September 2021. 

Rotolo A., Atherton M.J., Kasper B.T., Haran K.P., & Mason N.J. Genetic re-direction of canine primary T cells for clinical trial use in pet dogs with spontaneous cancer. STAR Protocols. December 2021. 

Lenz J.A., Assenmacher C-A., Costa V., Rau S., Keuler N.S., Louka K.L., Maki R.G., Durham A.C., Radaelli E. & Atherton M.J. Increased tumor infiltrating lymphocyte density is associated with favorable outcomes in a comparative study of canine histiocytic sarcoma. Cancer Immunology, Immunotherapy. April 2022. 

Atherton M.J., Rotolo A., Haran K.P., & Mason N.J. Case report: Clinical and serological hallmarks of cytokine release syndrome in a canine B cell lymphoma patient treated with autologous CAR-T cells. Frontiers in Veterinary Science. July 2022. 

Atherton M.J. & Mason N.M. Bitesize introduction to canine hematologic malignancies. Blood Advances. July 2022.  

Zhang H., Yu P., Tomar V., Atherton M.J., Lu Z., Ortiz A., Gui J., Leu N.A., Yan F., Blanco A., Meyer-Ficca M., Meyer R., Beiting D., Li J., Nunez-Cruz S., O'Connor R., Johnson L., Minn A., George S., Koumenis C., Diehl J.A., Milone M., Zheng H. & Fuchs S.Y. Targeting PARP11 to avert immunosuppression and improve CAR T therapy. Nature Cancer. July 2022.  

Gedney A., Salah P., Mahoney J.A., Krick E., Martins R., Scavello H., Lenz J.A. & Atherton M.J. Evaluation of the anti-tumor activity of Coriolus versicolor polysaccharopeptide (I’m Yunity®) alone or in combination with doxorubicin for canine splenic hemangiosarcoma. Veterinary and Comparative Oncology. September 2022. 

Chen J., Lu Z., Yu P., Atherton M.J., De Rosa G., Gui J., Tomar V.S., Middleton J., Sullivan N.T., Singhal S., George S.S., Hai T., Eruslanov E. & Fuchs S.Y. Tumor factors increase lysosomal activities to undermine antigen cross-presentation in lung cancer. Nature Communications. November 2022. 

Lenz J.A., Benjamin S.E., Walsh K.A., Keuler N.S., & Atherton M.J. Calculation of dose intensity & comparison of published methods using a cohort of canine T-cell lymphoma patients undergoing CHOP-based chemotherapy. Veterinary and Comparative Oncology. June 2023.  

Zimmerman K., Walsh K.A., Ferrari J.T., Keuler N.S., Atherton, M.J. & Lenz J.A. Evaluation of mechlorethamine, vinblastine, procarbazine, and prednisone (MVPP) for the treatment of resistant multicentric canine lymphoma. Veterinary and Comparative Oncology. September 2023.  

Rotolo A., Whelan E. C., Atherton M. J., Kulikovskaya I., Jarocha D., Fraietta J.A., Kim M. M., Diffenderfer E. S., Cengel K. A., Piviani M., Radaelli E., Duran-Struuck R., & Mason N. J.  Unedited allogeneic NKT cells show extended persistence in MHC-mismatched canine recipients. Cell Reports Medicine. October 2023.

Pre 2020: 

Atherton M.J. and Arthurs G. Osteosarcoma of the tibia 6 Years after tibial plateau leveling osteotomy. Journal of the American Animal Hospital Association. May/June 2012. 

Atherton M.J., Braceland M., Harvie J., Burchmore R.J., Eadie S., Eckersall P.D. & Morris J.S. Characterisation of the normal canine serum proteome using a novel electrophoretic technique combined with mass spectrometry. The Veterinary Journal. January 2013. 

Atherton M.J., Braceland M., Fontaine S., Waterston M.M., Burchmore R.J., Eadie S., Eckersall P.D. & Morris J.S. Changes in the serum proteome of canine lymphoma identified by electrophoresis and mass spectrometry. The Veterinary Journal. January 2013. 

Pratschke K.M., Atherton M.J., Sillito J.A. & Lamm C.G. Evaluation of a modified proportional margins approach for surgical resection of mast cell tumors in dogs: 40 cases (2008–2012). Journal of the American Veterinary Medical Association. November 2013. 

Atherton M.J. & Lichty B.D. Evolution of oncolytic viruses: novel strategies for cancer treatment. Immunotherapy. November 2013. 

Atherton M.J., Morris J.S., McDermott M.R. & Lichty B.D. Cancer immunology and canine malignant melanoma: A comparative review. Veterinary Immunology and Immunopathology. January 2016. 

Wang F., Alain T., Szretter K.J., Stephenson K., Pol J.G., Atherton M.J., Hoang H-D., Fonseca B.D., Zakaria C., Chen L., Rangwala Z., Hesch A., Sin Yan Chan E., Tuinman C., Suthar M.S., Jiang Z., Ashkar A.A., Thomas G., Kozma S.C., Gale M., Fitzgerald K.A., Diamond M.S., Mossman K., Sonenberg N., Wan Y. & Lichty B.D. S6K-STING interaction regulates cytosolic DNA-mediated IRF3 activation. Nature Immunology. April 2016. 

Atherton M.J., Vazquez‐Sanmartin S., Sharpe S., Waugh E.M. & Morris J.S. et al. A metastatic secretory gastric plasmacytoma with aberrant CD3 expression in a dog. Veterinary Clinical Pathology. September 2017. 

Atherton M.J., Stephenson K.B., Pol J., Wang F., Lefebvre C., Stojdl D.F., Nikota J.K., Dvorkin-Gheva A., Nguyen A., Chen L., Johnson-Obaseki S., Villeneuve P.J., Diallo J-S., Dimitroulakos J., Wan Y. & Lichty B.D. Customized viral immunotherapy for HPV-associated cancer. Cancer Immunology Research. October 2017. Featured as cover article and data was used to support initiation of phase I/Ib clinical trial NCT03618953. 

Carvalho S., Stoll A.L., Priestnall S.L., Suarez‐Bonnet A., Rassnick K., Lynch S., Schoepper I., Romanelli G., Buracco P., Atherton M.J., De Merlo E.M. & Lara‐Garcia A. Retrospective evaluation of COX-2 expression, histological and clinical factors as prognostic indicators in dogs with renal cell carcinomas undergoing nephrectomy. Veterinary and Comparative Oncology. December 2017. 

Atherton M.J., Evgin L., Keller B.A., Shenouda M.M., Stephenson K.B., Vile R.G., Bell J.C., Evans D.H. & Lichty B.D. Infectious Optimism Following The 10th International Oncolytic Virus Meeting. Molecular Therapy Oncolytics. December 2017. 

Atherton M.J., Stephenson K.B., Tzelepis F., Bakhshinyan D., Nikota J.K., Son H.H., Jirovec A., Lefebvre C., Dvorkin-Gheva A., Ashkar A.A., Wan Y., Stojdl D.F., Belanger E.C., Breau R.H., Bell J.C., Saad F., Singh S.K., Diallo J-S. & Lichty B.D. Transforming the prostatic tumor microenvironment with oncolytic virotherapy. OncoImmunology. March 2018. 

Atherton M.J., Stephenson K.B., Nikota J.K., Hu Q.N., Nguyen A., Wan Y. & Lichty B.D. Preclinical development of peptide vaccination combined with oncolytic MG1-E6E7 for HPV- associated cancer. Vaccine. April 2018. 

Pol J.G., Acuna S.A., Yadollahi B., Tang N., Stephenson K.B., Atherton M.J., Hanwell D., El-Warrak A., Goldstein A., Moloo B., Turner P.V., Lopez R., LaFrance S., Evelegh C., Denisova G., Parsons R., Millar J., Stoll G., Martin C.G., Pomoransky J., Breitbach C.J., Bramson J.L., Bell J.C., Wan Y., Stojdl D.F., Lichty B.D. & McCart J.A. Preclinical evaluation of a MAGE-A3 vaccination utilizing the oncolytic Maraba virus currently in first-in-human trials. OncoImmunology. January 2019.