About

Nicola J Mason is a professor in the Faculty of Biomedical Graduate Studies at the Perelman School of Medicine, University of Pennsylvania. She holds a B.Vet.Med degree from the University of London and a PhD in Immunology from the University of Pennsylvania. Her translational research program focuses on a comparative approach utilizing immunologically intact, canine patients with spontaneous cancer to evaluate the safety and effectiveness of next-generation immunotherapies. This approach aims to accelerate the translation of promising pre-clinical discoveries into human clinical applications. Dr. Mason's lab is actively involved in developing the canine model for evaluating CAR T cell therapies, translating strategies from lab and murine models into client-owned dogs suffering from lymphoma, osteosarcoma, and hemangiosarcoma. She leads clinical trials assessing immune-based therapies, including a recombinant Listeria vaccine to prevent metastatic disease in dogs with osteosarcoma, and coordinates the Canine Cancer Immunotherapy Trials as part of the Cancer Moonshot program. Her extensive experience includes methodologies for expanding and genetically modifying canine T cells ex vivo and conducting clinical trials using CART cells in dogs with B-cell non-Hodgkin lymphoma, performed at the University of Pennsylvania Veterinary Hospital.

Research topics

• Medicine
• Biology
• Immunology
• Cancer research
• Internal medicine

Selected publications

• Chemistry-mediated synthetic virus-cell interaction as a generic approach to enhance gene delivery to mammalian cells

  Molecular Therapy Advances · 2026-01-03

  articleOpen access
  PublisherOA PDFDOI

• Generation of functional canine TIL products for solid tumors

  Frontiers in Immunology · 2026-05-13

  articleOpen accessSenior author

  Immunotherapy based on the adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) has proven effective in treating human metastatic melanoma patients, but success in tumors with lower mutational burdens remains a challenge. Preclinical evaluation of cellular therapies commonly relies on murine models, which often require implantation of tumors into immunocompromised mice and thus do not accurately reflect the complex tumor-immune interactions seen in patients. Alternatively, spontaneous tumors in client-owned dogs serve as an underutilized and valuable parallel patient population for investigating the effectiveness of adoptive cell therapy in an immunocompetent host. However, TILs have been largely unexplored in dogs. Leveraging canine cancer patients with naturally occurring low tumor mutational burden (TMB) cancer types to study TIL therapy aims to enhance preclinical translatability. To evaluate the feasibility of TIL therapy in the veterinary sector, we developed protocols to reliably expand TILs from canine oral melanoma and appendicular osteosarcoma, despite low T cell frequencies in tumor digests. A subset of these TIL products showed reactivity to autologous tumor cells from fresh tumor digests as well as early passage cell lines. Lack of TIL reactivity in a beta-2-microglobulin (B2M)-ablated canine melanoma sample confirmed that recognition was major histocompatibility complex (MHC) class I-dependent. Together, these data establish the feasibility of generating functional canine TIL products and pave the way for comparative trials to evaluate TIL efficacy and novel strategies to enhance responses in low-TMB malignancies.

  PublisherDOI

• Combination radiation and Listeria immunotherapy induces cytotoxic immunity that correlates with improved outcome in dogs with osteosarcoma

  Molecular Therapy Oncology · 2026-05-01

  articleOpen access1st authorCorresponding
  PublisherDOI

• Innate iNKT cells: from biological insight to clinical impact

  Frontiers in Immunology · 2025-09-10 · 4 citations

  reviewOpen access

  Over the past 30 years, work of immunologists worldwide has phenotypically and functionally defined "Natural Killer T cells" (NKT) and their subsets, including "invariant Natural Killer T cells" (iNKT). NKT cells make up a substantial fraction of T cells that express NK cell markers and have TCRs restricted to either conventional MHC molecules or the monomorphic CD1d molecule. Among these, iNKT cells are CD1d-restricted and more common within NKT cells than T cells without NK markers. While the definition of NKT cells, whether based on phenotype, function, or both, remains a topic of debate, iNKT cells represent a distinct T cell population characterized by a recurrent, conserved TCR rearrangement (TRAV10-TRAJ18 in humans) paired with a limited Vβ repertoire (mostly encoded by TRBV25-1 in humans). iNKT cells are restricted by CD1d, which, unlike CD1a-c molecules, is expressed not only on professional antigen-presenting cells and thymocytes but also on certain non-hematopoietic somatic tissues, both normal and neoplastic. Like all CD1 family members, CD1d presents various lipid antigens by accommodating their long hydrophobic tails in deep binding pockets, in contrast to the shallow peptide grooves of conventional MHC molecules. However, the ligand repertoire of CD1d is distinct from that of CD1a-c. This review focuses on CD1d-restricted iNKT cells. Activation of iNKT cells via their semi-invariant TCR, often in synergy with NK receptors and other co-stimulatory molecules, triggers a rapid, polyfunctional response. Unlike conventional MHC-restricted T cells, individual iNKT cells can simultaneously produce both Th1- and Th2-type cytokines and exert cytotoxic activity in an immune synapse-directed fashion. Through this combination of direct cytotoxicity and cytokine-mediated immunomodulation, iNKTs can eliminate target cells while activating myeloid and other lymphoid populations to amplify immune responses. Their versatility has fueled growing interest in harnessing iNKT cells across inflammatory, infectious, and oncological diseases, where early-phase studies have demonstrated their safety and preliminary efficacy. Moreover, because they are restricted by the non-polymorphic CD1d molecule and possess immune-regulatory properties, iNKT cells lack graft-versus-host potential, making them ideal candidates for allogeneic, off-the-shelf therapies. This review summarizes how iNKT cells are being reimagined as innovative tools for immune intervention across a range of clinical settings.

  PublisherOA PDFDOI

• Comparative oncology in action: vignettes on immunotherapy development

  Veterinary oncology. · 2025-02-13 · 6 citations

  reviewOpen access

  Immunotherapeutic approaches to cancer treatment have gained significant traction in recent years, due in large part to the success of immune checkpoint inhibitors and T cell-based therapies. Comparative oncology is the study of naturally-occurring cancer in companion (pet) animals, mainly dogs, and is a powerful tool in cancer research and drug development. Given their intact, educated immune systems and natural co-evolution of tumor, microenvironment and stromal components, tumor-bearing pet dogs are an attractive species in which to explore these cellular interactions and test novel therapeutic approaches. Moreover, similarities between the canine and human immune systems support assessment of a wide variety of approaches, including antagonistic or agonistic antibodies directed at specific cellular targets, tumor vaccines, cell-based therapies, and combinations of these with conventional cancer treatments such as chemotherapy and radiotherapy. This manuscript provides specific examples of how canine immunotherapeutic studies informed an approach destined for human use, with an emphasis on study design, correlative immune assay development and application, and definition of biologic effect.

  PublisherOA PDFDOI

• FcεRγI promotes canine CD8 chimeric antigen receptor T cell cytotoxicity through a Syk-NF-κB axis

  Molecular Therapy · 2025-12-10

  articleOpen access

  Comparative oncology has advanced cancer immunotherapy, although cellular mechanisms governing chimeric antigen receptor T cell (CART) therapy in canines are poorly understood. In a first-in-canine trial, anti-CD20 CART with canine 4-1BB-CD3ζ (cBBζ) domains induced CD20-negative lymphoma outgrowth but did not persist or deplete B cells. Here we show that canine CARTs incorporating human BBζ (hBBζ) demonstrate superior therapeutic function, mediated by FcεRγI. hBBζ-CART showed greater cytolysis and CD8 T cell outgrowth than cBBζ-CART in repetitive killing assays and a canine B cell leukemia xenograft model. Transcriptional profiling revealed upregulation of FCER1G and innate-like genes in CD8 hBBζ versus cBBζ-CARTs. CRISPR-mediated FCER1G deletion and pharmacologic Syk/NF-κB inhibition indicated that Syk-NF-κB signaling regulates FcεRγI-mediated enhancement of hBBζ-CART cytotoxicity, associated with increased granzyme B and IFN-γ/TNF-α production. Syk-NF-κB signaling promotes FcεRγI expression in hBBζ CARTs, and CAR-TCR interactions potentiate NF-κB signaling to upregulate FcεRγI and enhance CART function. These studies identify a potent therapeutic subset of innate-like canine CARTs induced by hBBζ signaling, which holds potential to improve both canine and human CART therapy.

  PublisherDOI

• Immunological responses and clinical outcomes in dogs with osteosarcoma receiving standard therapy and a Listeria vaccine expressing HER2

  Molecular Therapy · 2025-02-15 · 9 citations

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Distinct glutamine metabolic pathways support mitochondrial function in canine T cells 4008

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description The function of chimeric antigen receptor T (CAR T) cells is closely linked to their metabolic profile. Strategies like media conditioning and genetic modifications have been designed to optimize CAR T cell fuel selection and enhance mitochondrial metabolism, improving persistence, reducing exhaustion, and increasing anti-tumor efficacy. Canine cancer patients – with tumors resembling human malignancies – are valuable models for assessing next-generation adoptive T cell therapies. Exploring species-specific barriers, including metabolic differences not addressed during manufacturing, would allow us to optimize canine CAR T cells and better translate these findings to human therapies. We hypothesize that glutamine, with a two-fold greater concentration in canine versus human plasma, uniquely supports mitochondrial function in canine T cells. Preliminary findings indicate that canine T cells utilize less glutamine for succinyl-CoA and acetyl-CoA synthesis than human T cells, yet increased glutamine availability generates larger mitochondrial volumes, suggesting enhanced biogenesis and remodeling. Ongoing Seahorse, flow cytometry, and functional studies aim to delineate species-specific differences in glutamine-driven mitochondrial function and oxidative phosphorylation. These findings will guide strategies to condition canine CAR T cells, improve persistence and anti-tumor efficacy, and inform metabolic differences relevant to interpreting results in this comparative model. Funding Sources Supported by the Mason Cancer Research Fund. Topic Categories Veterinary and Comparative Immunology (VET)

  PublisherOA PDFDOI

• The journey to diagnosis of wild-type transthyretin-mediated (ATTRwt) amyloidosis: a path with multisystem involvement

  Orphanet Journal of Rare Diseases · 2024-11-08 · 11 citations

  articleOpen access

  BACKGROUND: Wild-type and hereditary transthyretin-mediated amyloidosis (ATTRwt and ATTRv amyloidosis, respectively) are progressive, fatal diseases with a broad range of clinical presentations and multisystem effects. Despite having a higher prevalence, ATTRwt amyloidosis is less well characterized due to its non-hereditary nature, and its relatively poorer disease awareness delays diagnosis. Understanding of its natural history has evolved in recent years, but this is largely based on physician-collected data rather than patients' reports of their own experiences. A mixed methods approach was used to evaluate how the healthcare journeys of patients with ATTRv and ATTRwt amyloidosis compare. METHODS: A quantitative survey was administered to US-patients diagnosed with both ATTRwt amyloidosis and ATTRv amyloidosis identified through a patient support group. Subsequent in-depth interviews with participants with ATTRwt amyloidosis were conducted. Quantitative data with related qualitative quotes from patients were produced to characterize their paths to diagnosis and the disease burden experienced. RESULTS: A total of 47 respondents completed the survey (ATTRv, n = 20 and ATTRwt, n = 27) and a total of 14 survey respondents with ATTRwt amyloidosis were interviewed. Survey results reported a high disease burden for patients with both conditions, with patients with ATTRwt amyloidosis reporting more diagnoses and procedures prior to their final diagnosis. Interviews with participants with ATTRwt amyloidosis revealed that patients face a high symptomatic burden of disease. Diagnosis was often delayed due to three key factors: (1) early signs of ATTRwt amyloidosis were often assumed to be related to old age; (2) many medical specialists working in silos were involved in participants' diagnostic; and (3) there was a general lack of disease awareness. Early indicators such as carpal tunnel syndrome were often overlooked. Participants were typically diagnosed after the disease had progressed to include severe cardiac symptoms such as atrial fibrillation and severe shortness of breath. Sleep apnoea was also reported by a number of participants, with a considerable impact on quality of life. CONCLUSIONS: Our study provides insight into the overall impact of the patient journey on their quality of life and demonstrates how increased awareness of ATTRwt amyloidosis and more coordinated engagement with physicians could reduce the time to diagnosis.

  PublisherOA PDFDOI

• Immunotherapy with genetically engineered T cells holds promise for the treatment of nonmalignant diseases in the dog

  Journal of the American Veterinary Medical Association · 2024-04-15 · 2 citations

  article1st authorCorresponding

  The ability to genetically redirect the antigenic specificity of T cells using chimeric antigen receptors (CAR) has led to unprecedented durable clinical remissions in human patients with relapsed/refractory hematological malignancies. This remarkable advance in successful immune cell engineering has now led to investigations into the application of CAR-T-cell technology to treat nonmalignant diseases. The use of CAR-T cells to target and eliminate specific cell subsets involved in the pathogenesis of autoimmunity, fibrosis, senescence, and infectious disease represents a new direction for adoptive cell therapies. While the use of CAR-T cells for nonmalignant disease is still in its infancy, early reports of dramatic clinical responses to CAR-T cells targeting CD19+ B cells in patients with severe autoimmune disease raise the possibility that this approach could lead to durable remissions, eliminating the need for ongoing conventional immunosuppressive therapies. Excitingly, nonmalignant disease processes that may be addressed by CAR-T-cell therapy in humans also occur in our canine populations. Given that technologies for developing canine CAR constructs are now available, robust protocols have been described for generating canine CAR-T cells, and experience is being gathered with their clinical use in oncology, it is anticipated that CAR-T cells will soon enter the veterinary clinics for the treatment of debilitating nonmalignant diseases. Here, we provide a broad overview of CAR-T-cell therapies for nonmalignant diseases and extrapolate these advances into the veterinary space, highlighting areas in which canine CAR-T cells are poised to enter the clinics for the treatment of nonmalignant disease.

  PublisherDOI

Recent grants

• Translating cellular immunotherapies for autoimmunity to canine clinical trials

  NIH · $4.0M · 2018–2024

• NIH Grant K08AI050827

  NIH · $380k · 2005

Frequent coauthors

• Anita Gaurnier-Hausser

  32 shared

• Christina Coughlin

  21 shared

• Albert S. Baldwin

  20 shared

• Michael J. May

  University of Pennsylvania

  19 shared

• Reema Patel

  National Institutes of Health Clinical Center

  19 shared

• Avery D. Posey

  University of Pennsylvania

  18 shared

• Matthew J. Atherton

  University of Pennsylvania

  17 shared

• Josephine S. Gnanandarajah

  14 shared

Education

• Post-doctoral fellow, Abramson Family Cancer Research Institute

  University of Pennsylvania

  2006

• Resident in Internal Medicine, Clinical Sciences and Advanced Medicine

  University of Pennsylvania

  1997

• B.Vet.Med., Royal Veterinary College, University of London

  University of Pennsylvania

  1992