Stefanie R. Bailey
- Website: https://www.thebaileylab.com
Primary Appointment
Assistant Professor of Pediatrics, Pediatrics
Education
- PhD, Microbiology & Immunology, Medical University of South Carolina
- Postdoctoral Fellowship, Cellular Immunotherapy, Harvard Medical School, Massachusetts General Hospital
Research Disciplines
Cancer Biology, Cell and Developmental Biology, Immunology, Metabolism, Translational Science
Research Interests
Increasing the safety and efficacy of engineered T cells for patients with solid tumors
Research Description
Genetically engineering T cells with a chimeric antigen receptor (CAR) allows for recognition and subsequent destruction of cancer cells. While this has been a revolutionary treatment for many patients with B cell malignancies, several obstacles remain in the setting of relapsed/refractory disease and in solid tumors. Recent work has highlighted that a deeper mechanistic understanding of dogmas in the field, such as the importance of interferon gamma (IFNg) in cell-based therapies, can inform and improve future CAR-T therapies. Investigation of the dichotomous nature of IFNg has resulted in clinically-feasible approaches to increase the safety of CAR-T in hematologic malignancies, as well as improve the efficacy and persistence of CAR-T in solid tumors (Bailey, et al. Blood Cancer Discovery, 2022).
Building on this work, we will initially focus on understanding how cytokine crosstalk and intercellular interactions influence 1) CAR-T persistence, metabolism and anti-tumor activity and 2) the immunosuppressive nature of the tumor microenvironment . Given the significant potential for CD4+ T cells in CAR-T (Bailey, et al. Nature Communications, 2017), as well as their tendency to be over-looked in cell therapy, we are particularly interested in exploring and capitalizing on this subset. Collectively, our team aims to leverage mechanistic discoveries to thoughtfully design and improve CAR-T therapies for children with cancer.
Selected Publications
2024
Korell, F., Olson, M. L., Salas-Benito, D., Leick, M. B., Larson, R. C., Bouffard, A., . . . Maus, M. V. (2024). Comparative analysis of Bcl-2 family protein overexpression in CAR T cells alone and in combination with BH3 mimetics. SCIENCE TRANSLATIONAL MEDICINE, 16(750). doi:10.1126/scitranslmed.adk7640
Wehrli, M., Guinn, S., Birocchi, F., Kuo, A., Sun, Y., Larson, R. C., . . . Maus, M. V. (2024). Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma. CLINICAL CANCER RESEARCH, 30(9), 1859-1877. doi:10.1158/1078-0432.CCR-23-3841
2023
Bailey, S. R., Berger, T. R., Graham, C., Larson, R. C., & Maus, M. V. (2023). Four challenges to CAR T cells breaking the glass ceiling. European Journal of Immunology, 53(11). doi:10.1002/eji.202250039
Pourzia, A. L., Olson, M. L., Bailey, S. R., Boroughs, A. C., Aryal, A., Ryan, J., . . . Letai, A. (2023). Quantifying requirements for mitochondrial apoptosis in CAR T killing of cancer cells. CELL DEATH & DISEASE, 14(4). doi:10.1038/s41419-023-05727-x
Schmidts, A., Srivastava, A. A., Ramapriyan, R., Bailey, S. R., Bouffard, A. A., Cahill, D. P., . . . Choi, B. D. (2023). Tandem chimeric antigen receptor (CAR) T cells targeting EGFRvIII and IL-13Rα2 are effective against heterogeneous glioblastoma. Neuro-Oncology Advances, 5(1). doi:10.1093/noajnl/vdac185
2022
Leick, M. B., Silva, H., Scarfò, I., Larson, R., Choi, B. D., Bouffard, A. A., . . . Maus, M. V. (2022). Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia. Cancer Cell, 40(5), 494-508.e5. doi:10.1016/j.ccell.2022.04.001
Larson, R. C., Kann, M. C., Bailey, S. R., Haradhvala, N. J., Llopis, P. M., Bouffard, A. A., . . . Maus, M. V. (2022). CAR T cell killing requires the IFNγR pathway in solid but not liquid tumours. NATURE, 604(7906), 563-+. doi:10.1038/s41586-022-04585-5
Bailey, S. R., Vatsa, S., Larson, R. C., Bouffard, A. A., Scarfo, I., Kann, M. C., . . . Maus, M. V. (2022). Blockade or Deletion of IFNγ Reduces Macrophage Activation without Compromising CAR T-cell Function in Hematologic Malignancies. BLOOD CANCER DISCOVERY, 3(2), 136-153. doi:10.1158/2643-3230.BCD-21-0181
2020
Nelson, M. H., Knochelmann, H. M., Bailey, S. R., Huff, L. W., Bowers, J. S., Majchrzak-Kuligowska, K., . . . Paulos, C. M. (2020). Identification of human CD4
+
T cell populations with distinct antitumor activity. Science Advances, 6(27). doi:10.1126/sciadv.aba7443
2019
Choi, B. D., Yu, X., Castano, A. P., Darr, H., Henderson, D. B., Bouffard, A. A., . . . Maus, M. V. (2019). CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma. Journal for ImmunoTherapy of Cancer, 7(1). doi:10.1186/s40425-019-0806-7
Ormhoj, M., Scarfo, I., Cabral, M. L., Bailey, S. R., Lorrey, S. J., Bouffard, A. A., . . . Maus, M. V. (2019). Chimeric Antigen Receptor T Cells Targeting CD79b Show Efficacy in Lymphoma with or without Cotargeting CD19. CLINICAL CANCER RESEARCH, 25(23), 7046-7057. doi:10.1158/1078-0432.CCR-19-1337
Bowers, J. S., Bailey, S. R., Rubinstein, M. P., Paulos, C. M., & Camp, E. R. (n.d.). Genomics meets immunity in pancreatic cancer: Current research and future directions for pancreatic adenocarcinoma immunotherapy. Oncology Reviews, 13(2). doi:10.4081/oncol.2019.430
Choi, B. D., Yu, X., Castano, A. P., Bouffard, A. A., Schmidts, A., Larson, R. C., . . . Maus, M. V. (2019). CAR-T cells secreting BiTEs circumvent antigen escape without detectable toxicity. NATURE BIOTECHNOLOGY, 37(9), 1049-+. doi:10.1038/s41587-019-0192-1
Bailey, S. R., & Maus, M. V. (2019). Gene editing for immune cell therapies. NATURE BIOTECHNOLOGY, 37(12), 1425-1434. doi:10.1038/s41587-019-0137-8
2018
Knochelmann, H. M., Dwyer, C. J., Bailey, S. R., Amaya, S. M., Elston, D. M., Mazza-McCrann, J. M., & Paulos, C. M. (2018). When worlds collide: Th17 and Treg cells in cancer and autoimmunity. CELLULAR & MOLECULAR IMMUNOLOGY, 15(5), 458-469. doi:10.1038/s41423-018-0004-4
2017
Bailey, S. R., Nelson, M. H., Majchrzak, K., Bowers, J. S., Wyatt, M. M., Smith, A. S., . . . Paulos, C. M. (2017). Human CD26high T cells elicit tumor immunity against multiple malignancies via enhanced migration and persistence. NATURE COMMUNICATIONS, 8. doi:10.1038/s41467-017-01867-9
Majchrzak, K., Nelson, M. H., Bowers, J. S., Bailey, S. R., Wyatt, M. M., Wrangle, J. M., . . . Paulos, C. M. (2017). β-catenin and PI3Kδ inhibition expands precursor Th17 cells with heightened stemness and antitumor activity. JCI INSIGHT, 2(8). doi:10.1172/jci.insight.90547
Zhu, P., Bailey, S. R., Lei, B., Paulos, C. M., Atkinson, C., & Tomlinson, S. (2017). Targeted Complement Inhibition Protects Vascularized Composite Allografts From Acute Graft Injury and Prolongs Graft Survival When Combined With Subtherapeutic Cyclosporine A Therapy. TRANSPLANTATION, 101(4), E75-E85. doi:10.1097/TP.0000000000001625
Bowers, J. S., Nelson, M. H., Majchrzak, K., Bailey, S. R., Rohrer, B., Kaiser, A. D. M., . . . Paulos, C. M. (2017). Th17 cells are refractory to senescence and retain robust antitumor activity after long-term ex vivo expansion. JCI INSIGHT, 2(5). doi:10.1172/jci.insight.90772
Neal, L. R., Bailey, S. R., Wyatt, M. M., Bowers, J. S., Majchrzak, K., Nelson, M. H., . . . Varela, J. C. (2017). The Basics of Artificial Antigen Presenting Cells in T Cell-Based Cancer Immunotherapies.. Journal of immunology research and therapy, 2(1), 68-79.
Bowers, J. S., Majchrzak, K., Nelson, M. H., Aksoy, B. A., Wyatt, M. M., Smith, A. S., . . . Paulos, C. M. (2017). Pl3Kδ Inhibition Enhances the Antitumor Fitness of Adoptively Transferred CD8+ T Cells. FRONTIERS IN IMMUNOLOGY, 8. doi:10.3389/fimmu.2017.01221
2016
Majchrzak, K., Nelson, M. H., Bailey, S. R., Bowers, J. S., Yu, X. -Z., Rubinstein, M. P., . . . Paulos, C. M. (2016). Exploiting IL-17-producing CD4+ and CD8+ T cells to improve cancer immunotherapy in the clinic. CANCER IMMUNOLOGY IMMUNOTHERAPY, 65(3), 247-259. doi:10.1007/s00262-016-1797-6
Nelson, M. H., Bowers, J. S., Bailey, S. R., Diven, M. A., Fugle, C. W., Kaiser, A. D. M., . . . Paulos, C. M. (2016). Toll-like receptor agonist therapy can profoundly augment the antitumor activity of adoptively transferred CD8+ T cells without host preconditioning. JOURNAL FOR IMMUNOTHERAPY OF CANCER, 4. doi:10.1186/s40425-016-0110-8
2015
Bowers, J. S., Nelson, M. H., Kundimi, S., Bailey, S. R., Huff, L. W., Schwartz, K. M., . . . Paulos, C. M. (2015). Dendritic Cells in Irradiated Mice Trigger the Functional Plasticity and Antitumor Activity of Adoptively Transferred Tc17 Cells via IL12 Signaling. CLINICAL CANCER RESEARCH, 21(11), 2546-2557. doi:10.1158/1078-0432.CCR-14-2294
2014
Chatterjee, S., Thyagarajan, K., Kesarwani, P., Song, J. H., Soloshchenko, M., Fu, J., . . . Mehrotra, S. (2014). Reducing CD73 Expression by IL1β-Programmed Th17 Cells Improves Immunotherapeutic Control of Tumors. CANCER RESEARCH, 74(21), 6048-6059. doi:10.1158/0008-5472.CAN-14-1450
Bailey, S. R., Nelson, M. H., Himes, R. A., Li, Z., Mehrotra, S., & Paulos, C. M. (2014). Th17 cellsin cancer: the ultimate identity crisis. FRONTIERS IN IMMUNOLOGY, 5. doi:10.3389/fimmu.2014.00276