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Michael C. Milone, M.D., Ph.D.
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Associate Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
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Staff Physician, Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania
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Associate Director, Toxicology and Mass Spectrometry Laboratory
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Associate Vice Chair for Profession Development and Academic Affairs, Department of Pathology and Laboratory Medicine, Perelman School of Medicine,
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Department: Pathology and Laboratory Medicine
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Graduate Group Affiliations
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- Cell and Molecular Biology 6a
- Pharmacology 5c
- Immunology e
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Contact information
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3400 Spruce Street 7103 Founders Pavilion
Philadelphia, PA 19104
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Philadelphia, PA 19104
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Office: 215-662-6575
32 Fax: 215-662-7529
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32 Fax: 215-662-7529
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Publications
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Education:
21 8 B.S 1d (Chemical Biology) c
38 Stevens Institute of Technology, 1993.
21 9 Ph.D 2f (Experimental Pathology/ Immunology) c
47 UMDNJ - Graduate School of Biomedical Sciences, 1999.
21 9 M.D. 1b (Medical Doctor) c
39 UMDNJ- New Jersey Medical School, 1999.
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Permanent link21 8 B.S 1d (Chemical Biology) c
38 Stevens Institute of Technology, 1993.
21 9 Ph.D 2f (Experimental Pathology/ Immunology) c
47 UMDNJ - Graduate School of Biomedical Sciences, 1999.
21 9 M.D. 1b (Medical Doctor) c
39 UMDNJ- New Jersey Medical School, 1999.
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3a Active research projects in my laboratory include:
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a3 1) Developing chimeric antigen receptors (CARs) and other engineering approaches for enhancing the function and improved safety of adoptive T cell therapy.
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69 2) Developing and applying synthetic immunoreceptors to the treatment of immune-mediated disease.
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98 3) Exploring the role of co-stimulatory signals in directing T cell metabolism and the way this metabolism affects T cell function within tumors.
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Description of Research Expertise
99 Research in my laboratory is focused on T cell biology and applications of genetically-engineered T cells to the treatment of disease.8
3a Active research projects in my laboratory include:
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a3 1) Developing chimeric antigen receptors (CARs) and other engineering approaches for enhancing the function and improved safety of adoptive T cell therapy.
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69 2) Developing and applying synthetic immunoreceptors to the treatment of immune-mediated disease.
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98 3) Exploring the role of co-stimulatory signals in directing T cell metabolism and the way this metabolism affects T cell function within tumors.
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Description of Clinical Expertise
9a Clinical Laboratory Toxicology, Therapeutic Drug Monitoring, Clinical Chemistry, Blood Banking/Transfusion Medicine, Therapeutic Apheresis1a 29
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1a0 Engel NW, Steinfeld I, Ryan D, Anupindi K, Kim S, Wellhausen N, Chen L, Wilkins K, Baker DJ, Rommel PC, Jarocha D, Gohil M, Zhang Q, Milone MC, Fraietta JA, Davis M, Young RM, June CH.: Quadruple adenine base-edited allogeneic CAR T cells outperform CRISPR/Cas9 nuclease-engineered T cells. Proc Natl Acad Sci U S A 122: e2427216122, May 2025.
126 Balis FM, Rieger E, Bunin NJ, Gardiner J, Shaw LM, Olson TS, Milone MC.: New approach to busulfan dosing in infants and children based on a population pharmacokinetic analysis. Cancer Chemother Pharmacol 95: 32, Feb 2025.
268 Zhang, Qian, Wu, Yihao, Yang, Jingyi, Zhou, Kevin, Anand Manoharan, Eric Nigel Ebenezer, Wentz, Tyra, Su, Leon, Yu, Alvin, Wang, Hong-Yi, Bruhn, Laurakay, Steinfeld, Israel, Gonzalez, Nicolas, Song, Edward Z., Zhang, Yunlin, Hresko, Morgan E., Ryan, Daniel E., Engel, Nils W., Nunez-Cruz, Selene, June, Carl H., Garcia, K. Christopher, Milone, Michael C.: Viral vector-free generation of orthogonal IL-2–responsive CAR T cells through gene editing of IL-2 and its receptor. Blood Immunology & Cellular Therapy 1(3), 2025.
297 Ghilardi, G., Paruzzo, L., Svoboda, J., Chong, E. A., Shestov, A. A., Chen, L., Cohen, I. J., Gabrielli, G., Nasta, S. D., Porazzi, P., Landsburg, D. J., Gerson, J. N., Carter, J., Barta, S. K., Yelton, R., Pajarillo, R., Patel, V., White, G., Ballard, H. J., Weber, E., Napier, E., Chong, E. R., Fraietta, J. A., Garfall, A. L., Porter, D. L., Milone, M. C., O'Connor, R., Schuster, S. J., Ruella, M.: Bendamustine lymphodepletion before axicabtagene ciloleucel is safe and associates with reduced inflammatory cytokines. Blood Adv 8(3): 653-666, February 2024.
1f6 Zhang Z, Markmann C, Yu M, Agarwal D, Rostami S, Wang W, Liu C, Zhao H, Ochoa T, Parvathaneni K, Xu X, Li E, Gonzalez V, Khadka R, Hoffmann J, Knox JJ, Scholler J, Marcellus B, Allman D, Fraietta JA, Samelson-Jones B, Milone MC, Monos D, Garfall AL, Naji A, Bhoj VG.: Immunotherapy targeting B cells and long-lived plasma cells effectively eliminates pre-existing donor-specific allo-antibodies. Cell Rep Med 4: 101336, Dec 2023.
11b Grover P, Nunez-Cruz S, Leferovich J, Wentz T, Bagchi A, Milone MC, Greene MI.: F77 antigen is a promising target for adoptive T cell therapy of prostate cancer. Biochem Biophys Res Commun 680: 51-60, Nov 2023.
1dc Oh S, Mao X, Manfredo-Vieira S, Lee J, Patel D, Choi EJ, Alvarado A, Cottman-Thomas E, Maseda D, Tsao PY, Ellebrecht CT, Khella SL, Richman DP, O'Connor KC, Herzberg U, Binder GK, Milone MC, Basu S, Payne AS.: Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. Nat Biotechnol 41(9): 1229-1238, Sept 2023.
194 Glisovic-Aplenc, T., Diorio, C., Chukinas, J. A., Veliz, K., Shestova, O., Shen, F., Nunez-Cruz, S., Vincent, T. L., Miao, F., Milone, M. C., June, C. H., Teachey, D. T., Tasian, S. K., Aplenc, R., Gill, S.: CD38 as a pan-hematologic target for chimeric antigen receptor T cells. Blood Adv 7(16): 4418-4430, Aug 2023.
16c Thakrar AP, Faude S, Perrone J, Milone MC, Lowenstein M, Snider CK, Spadaro A, Delgado MK, Nelson LS, Kilaru AS.: Association of Urine Fentanyl Concentration With Severity of Opioid Withdrawal Among Patients Presenting to the Emergency Department. J Addict Med 17(4): 447-453, July-Aug 2023.
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Selected Publications
321 Liu, S., Guruprasad, P., Ramasubramanian, R., Madhu, B., Paruzzo, L., Han, K., Kelly, A., Shestov, A., Xu, H. N., Carturan, A., Zhou, C., Amses, K. R., Afriat, A., Litichevskiy, L., Lin, J., Dubowitz, E., Tangal, N., Zhang, J., McSween, A., Tan, M., Stella, F., Lee, A., Nason, S., Hua, X., Schneider, M., Sleeman, M., Zhang, Y., Gabrielli, G., Yang, Z., Pajarillo, R., Patel, R., Ghilardi, G., Patel, V., Joshi, A., Jiang, S., Jiang, Y., Porazzi, P., Tchou, J. C., Keith, B., Li, M., Chong, E., Schuster, S. J., Milone, M., Rabinowitz, J., O'Connor, R. S., Thaiss, C. A., Levy, M., Ruella, M.: β-hydroxybutyrate enhances the metabolic fitness of CAR T cells in cancer. Cell 2026.1a0 Engel NW, Steinfeld I, Ryan D, Anupindi K, Kim S, Wellhausen N, Chen L, Wilkins K, Baker DJ, Rommel PC, Jarocha D, Gohil M, Zhang Q, Milone MC, Fraietta JA, Davis M, Young RM, June CH.: Quadruple adenine base-edited allogeneic CAR T cells outperform CRISPR/Cas9 nuclease-engineered T cells. Proc Natl Acad Sci U S A 122: e2427216122, May 2025.
126 Balis FM, Rieger E, Bunin NJ, Gardiner J, Shaw LM, Olson TS, Milone MC.: New approach to busulfan dosing in infants and children based on a population pharmacokinetic analysis. Cancer Chemother Pharmacol 95: 32, Feb 2025.
268 Zhang, Qian, Wu, Yihao, Yang, Jingyi, Zhou, Kevin, Anand Manoharan, Eric Nigel Ebenezer, Wentz, Tyra, Su, Leon, Yu, Alvin, Wang, Hong-Yi, Bruhn, Laurakay, Steinfeld, Israel, Gonzalez, Nicolas, Song, Edward Z., Zhang, Yunlin, Hresko, Morgan E., Ryan, Daniel E., Engel, Nils W., Nunez-Cruz, Selene, June, Carl H., Garcia, K. Christopher, Milone, Michael C.: Viral vector-free generation of orthogonal IL-2–responsive CAR T cells through gene editing of IL-2 and its receptor. Blood Immunology & Cellular Therapy 1(3), 2025.
297 Ghilardi, G., Paruzzo, L., Svoboda, J., Chong, E. A., Shestov, A. A., Chen, L., Cohen, I. J., Gabrielli, G., Nasta, S. D., Porazzi, P., Landsburg, D. J., Gerson, J. N., Carter, J., Barta, S. K., Yelton, R., Pajarillo, R., Patel, V., White, G., Ballard, H. J., Weber, E., Napier, E., Chong, E. R., Fraietta, J. A., Garfall, A. L., Porter, D. L., Milone, M. C., O'Connor, R., Schuster, S. J., Ruella, M.: Bendamustine lymphodepletion before axicabtagene ciloleucel is safe and associates with reduced inflammatory cytokines. Blood Adv 8(3): 653-666, February 2024.
1f6 Zhang Z, Markmann C, Yu M, Agarwal D, Rostami S, Wang W, Liu C, Zhao H, Ochoa T, Parvathaneni K, Xu X, Li E, Gonzalez V, Khadka R, Hoffmann J, Knox JJ, Scholler J, Marcellus B, Allman D, Fraietta JA, Samelson-Jones B, Milone MC, Monos D, Garfall AL, Naji A, Bhoj VG.: Immunotherapy targeting B cells and long-lived plasma cells effectively eliminates pre-existing donor-specific allo-antibodies. Cell Rep Med 4: 101336, Dec 2023.
11b Grover P, Nunez-Cruz S, Leferovich J, Wentz T, Bagchi A, Milone MC, Greene MI.: F77 antigen is a promising target for adoptive T cell therapy of prostate cancer. Biochem Biophys Res Commun 680: 51-60, Nov 2023.
1dc Oh S, Mao X, Manfredo-Vieira S, Lee J, Patel D, Choi EJ, Alvarado A, Cottman-Thomas E, Maseda D, Tsao PY, Ellebrecht CT, Khella SL, Richman DP, O'Connor KC, Herzberg U, Binder GK, Milone MC, Basu S, Payne AS.: Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. Nat Biotechnol 41(9): 1229-1238, Sept 2023.
194 Glisovic-Aplenc, T., Diorio, C., Chukinas, J. A., Veliz, K., Shestova, O., Shen, F., Nunez-Cruz, S., Vincent, T. L., Miao, F., Milone, M. C., June, C. H., Teachey, D. T., Tasian, S. K., Aplenc, R., Gill, S.: CD38 as a pan-hematologic target for chimeric antigen receptor T cells. Blood Adv 7(16): 4418-4430, Aug 2023.
16c Thakrar AP, Faude S, Perrone J, Milone MC, Lowenstein M, Snider CK, Spadaro A, Delgado MK, Nelson LS, Kilaru AS.: Association of Urine Fentanyl Concentration With Severity of Opioid Withdrawal Among Patients Presenting to the Emergency Department. J Addict Med 17(4): 447-453, July-Aug 2023.
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