Janos L. Tanyi
· M.D., Ph.D.VerifiedUniversity of Pennsylvania · Rehabilitation Medicine
Active 1997–2026
About
Janos L. Tanyi, M.D., Ph.D., is an Associate Professor of Obstetrics and Gynecology at the Hospital of the University of Pennsylvania. He is an attending physician in Gynecologic Oncology at the same hospital, located in Philadelphia, PA. Dr. Tanyi completed his medical degree (M.D.) with Summa cum Laude from the University of Debrecen, Faculty of Medicine in Hungary in 1993, and earned his Ph.D. with Summa cum Laude from Semmelweis University, Faculty of Medicine, School of Clinical Sciences, Budapest, Hungary, in 2008. His professional focus is on gynecologic cancers, with a particular emphasis on ovarian cancer research and treatment.
Research topics
- Chemistry
- Pathology
- Medicine
- Internal medicine
Selected publications
Molecular Therapy · 2026-01-21 · 1 citations
articleOpen accessSenior authorCell Reports · 2026-01-21
articleOpen accessAs human populations migrated to diverse geographical regions, they encountered varying pathogens, leading to pronounced natural selection pressures on the immune system. Analysis of non-synonymous single-nucleotide polymorphisms (nsSNPs) across major geographically structured populations showed greater variation in immune-related genes than in non-immune genes, consistent with pathogen-driven selection, whereas cancer-related genes exhibited lower variation, reflecting the evolutionary conservation of critical cellular functions. We prioritized nsSNPs in pattern recognition receptor genes based on population diversity and their association with type I interferon (IFN) activity. Among the top-ranked variants were rs11554776, rs78233829, and rs7380824 in STING1, which demonstrated functional impacts on intrinsic cGAS-STING1-IFN signaling in cancer cells and potential influences on tumor immunity. We further conducted a genome-wide characterization of nsSNPs in immune-related genes across genetic ancestry populations and established a publicly accessible database. Our study suggests that genetic ancestry-related germline variations may influence cancer immunity and treatment, supporting their consideration in personalized medicine.
Cancer Research · 2026-04-17
article1st authorCorrespondingAbstract SynKIR-110 is a novel mesothelin-targeting autologous chimeric antigen receptor (CAR) T cell modeled after multichain immune receptors derived from natural killer cells, used in a first in human (FIH) phase 1 clinical trial to treat patients with advanced mesothelin-expressing solid tumors. Mesothelin-targeting single-chain variable fragment SS1 was recombined with killer-immunoglobulin-like receptor (KIR), which interacts with DNAX-activation protein of 12 kDa (DAP12) to induce effector T cell function. Preclinical studies with KIR-CAR showed decreased PD1 and Tim3 T cell exhaustion markers, with increased in vivo antitumor activity and decreased cytokine secretion compared with conventional CAR T. In this study, we assessed the safety and activity of SynKIR-110 in patients. A phase 1 dose-escalation study in patients with advanced ovarian cancer, mesothelioma, or cholangiocarcinoma who were refractory to standard of care treatment was conducted at four medical centers in the United States. Patients in dose cohorts 1-3 received a single intravenous dose of 1, 3, or 10 × 107 transduced SynKIR-110 T cells/m2, respectively, following lymphodepletion (LD) with cyclophosphamide and fludarabine; follow-up was for 12 months or until disease progression. Primary endpoints included safety and determination of a maximum tolerated dose (MTD) for a dose-expansion to evaluate anti-tumor activity. Circulating biomarkers were used to measure SynKIR-110 persistence and T cell activation. Clinical responses were evaluated via computed-tomography imaging starting 28 days after treatment. This ongoing study is registered with ClinicalTrials.gov NCT05568680. In cohorts 1-3, no dose-limiting toxicities or events meeting protocol-defined stopping criteria were reported. Three of 9 (33%) patients treated experienced low-grade cytokine release syndrome (≤grade 2), with no immune effector cell-associated neurologic events (0/9). Five of 9 (56%) patients experienced hematologic adverse events related to LD chemotherapy. SynKIR-110 was quantified in peripheral blood and increased with dosage, reaching peak levels >20,000 copies/µg DNA in cohorts 2 and 3, approximately 7 days after cell infusion. Effector T cell cytokines including interferon-gamma and tumor necrosis factor-alpha, reached peak serum concentration between 7 and 14 days after treatment, consistent with expectations for CAR T class therapies. Tumor responses were seen in 4 of 9 patients, up to 47% reduction for 1 patient each in cohorts 1 and 2, and 2 patients in cohort 3, one of whom maintained an iRECIST partial response through 6 months of follow-up. SynKIR-110 mesothelin-targeted KIR-CAR treatment showed a favorable safety profile, with notable clinical activity in the first 3 of 6 planned dose cohorts, in heavily pretreated patients with refractory mesothelin-expressing advanced solid tumors. MTD was not reached and dose-escalation enrollment is ongoing in this phase 1 FIH trial. Funding: Verismo Therapeutics Citation Format: Janos L. Tanyi, Andrew Haas, Mark O'Hara, Zhubin Gahvari, Raed Al-Rajabi, Mehmet Altan, Daniel Sterman, Emily Winters, Andrea Campanile, Susan Howard, Raymond Luke, Tony Truong, Megan Blair, Nora Yucel, Jun Xu, Don L. Siegel, Carl H. June, Michael C. Milone, Laura A. Johnson. Initial results of a first in human dose-escalation study of KIR-CAR in patients with advanced mesothelin-expressing solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT104.
Cancer Research · 2026-04-03
articleAbstract Introduction: Complete responses to PARP inhibitor (PARPi) monotherapy in recurrent high-grade serous ovarian cancer (HGSOC) are rare. However, preclinical data have demonstrated promising synergy between PARP and ATR inhibitors. Characterizing the immune contexture of the tumor microenvironment and the surrounding stroma during treatment may provide valuable biological insights into the efficacy of this combination therapy and inform future combinations. Methods: Patients with recurrent HGSOC received ceralasertib 160mg orally daily, days 1-7 and olaparib 300mg twice daily, days 1-28 of a 28-day cycle. 18 tissue samples were collected across archival (resection) and pre-treatment and on-treatment timepoints (core biopsies). Each sample was analyzed using a 25-plex multiplex immunohistochemistry (mIHC) assay, which interrogates cell composition and functional states of neoplastic and immune cell types, including all major lymphoid and myeloid populations. Segmented cells were assigned to either a tumor or stroma compartment using a PanCK mask that was uniformly expanded by 25μm, and average cell densities were calculated for each compartment. Results: Samples obtained during combination PARPi + ATRi treatment demonstrated widespread increases in immune cell densities including T cells (CD8+, Tregs, and Th1-like cells), B cells, dendritic cells, macrophages, and monocytes. Among the T-cell populations, higher densities of Granzyme B and PD-1 were observed, indicating enhanced cytotoxic activity and immune engagement. Concurrently, there was a decrease in proliferating neoplastic cells (PanCK+Ki67+), consistent with reduced tumor cell proliferation during treatment. Using the PanCK tumor mask, we observed that CD8+ T cells, Th1-like cells, B cells, and dendritic cells increased more prominently within the tumor compartment compared to the surrounding stroma. Samples obtained prior to treatment from patients with stable or progressive disease (SD/PD) exhibited higher macrophage densities, primarily attributable to elevated levels of M2-like (immunosuppressive) macrophages. Conclusions: The increased immune cell densities measured by mIHC indicate overall activation of the immune system following PARPi + ATRi treatment. Elevated levels of PD-1+ and Granzyme B+ T cells suggest enhanced immune activation and cytotoxic potential, while comparative analysis of the tumor versus stroma compartments demonstrates improved immune cell infiltration into the tumor. Notably, higher baseline densities of M2-like macrophages may influence or limit response to therapy. Collectively, these findings provide evidence that PARPi + ATRi combination therapy promotes anti-tumor immune activity. However, additional data is needed to correlate these immune changes with clinical outcomes. Citation Format: Elias Pavlatos, Benjamin Tate, Austin Nguyen, Ian S. Heller, Dimitrios Nasioudis, Janos L. Tanyi, Drew A. Torigian, Diego Rodriguez, Susan M. Domchek, Ronny I. Drapkin, Eric J. Brown, Gordon B. Mills, Fiona Simpkins. Increased immune activity in patients with high-grade serious ovarian cancer after combination PARPi + ATRi therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7749.
2025-11-25
articleOpen access<p>Trial schema</p>
eLife · 2025-07-09
preprintOpen accessAbstract Therapeutic epigenetic modulation is currently being evaluated in the clinic to sensitize homologous recombination (HR)-proficient tumors to PARP inhibitors. To broaden its clinical applicability and identify more effective combination strategies, we conducted a drug screen combining PARP inhibitors with 74 well-characterized epigenetic modulators targeting five major classes of epigenetic enzymes. Notably, both type I PRMT inhibitors and PRMT5 inhibitors scored highly in combination efficacy and clinical prioritization. PRMT inhibition significantly enhanced PARP inhibitor-induced DNA damage in HR-proficient ovarian and breast cancer cells. Mechanistically, PRMT suppression downregulates DNA damage repair genes and BRCAness-associated pathways, while also modulating intrinsic innate immune responses within cancer cells. Integrative analysis of large-scale genomic and functional datasets from TCGA and DepMap further supports PRMT1, PRMT4, and PRMT5 as promising therapeutic targets in oncology. Importantly, dual inhibition of PRMT1 and PRMT5 synergistically sensitizes tumors to PARP inhibitors. Collectively, our findings provide strong rationale for the clinical development of PRMT and PARP inhibitor combinations in HR-proficient ovarian and breast cancers.
Clinical and molecular dissection of CAR T cell resistance in pancreatic cancer
Cell Reports Medicine · 2025-08-18 · 8 citations
articleOpen accessphenotype. Single knockout of ID3 or SOX4 enhances efficacy in xenograft models, though with donor-dependent variability. However, single-knockout cells eventually fail. Conversely, ID3 and SOX4 double-knockout CAR T cells exhibit prolonged relapse-free survival, demonstrating a sustained therapeutic effect and a potential avenue for engineering more potent CAR T cells in PDAC. This study was registered at ClinicalTrials.gov (NCT03323944).
2025-11-25
articleOpen access<p>Clinical response correlates.</p>
eLife · 2025-09-26
articleOpen accessAbstract Therapeutic epigenetic modulation is currently being evaluated in the clinic to sensitize homologous recombination (HR)-proficient tumors to PARP inhibitors. To broaden its clinical applicability and identify more effective combination strategies, we conducted a drug screen combining PARP inhibitors with 74 well-characterized epigenetic modulators targeting five major classes of epigenetic enzymes. Notably, both type I PRMT inhibitors and PRMT5 inhibitors scored highly in combination efficacy and clinical prioritization. PRMT inhibition significantly enhanced PARP inhibitor-induced DNA damage in HR-proficient ovarian and breast cancer cells. Mechanistically, PRMT suppression downregulates DNA damage repair genes and BRCAness-associated pathways, while also modulating intrinsic innate immune responses within cancer cells. Integrative analysis of large-scale genomic and functional datasets from TCGA and DepMap further supports PRMT1, PRMT4, and PRMT5 as promising therapeutic targets in oncology. Importantly, dual inhibition of PRMT1 and PRMT5 synergistically sensitizes tumors to PARP inhibitors. Collectively, our findings provide strong rationale for the clinical development of PRMT and PARP inhibitor combinations in HR-proficient ovarian and breast cancers.
2025-11-25
articleOpen access<p>Representativeness of Study Participants</p>
Frequent coauthors
- 202 shared
Mark A. Morgan
- 153 shared
Setsuko K. Chambers
University of Arizona Cancer Center
- 152 shared
Alexander L. Vahrmeijer
Leiden University Medical Center
- 152 shared
Leslie M. Randall
- 151 shared
Robert M. Wenham
- 150 shared
Kristina Butler
- 150 shared
Carrie Langstraat
- 149 shared
Matthew A. Powell
Washington University in St. Louis
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