Faculty

Michael C. Milone, M.D., Ph.D.

faculty photo
Associate Professor of Pathology and Laboratory Medicine at the Hospital of the University of Pennsylvania
Department: Pathology and Laboratory Medicine
Graduate Group Affiliations

Contact information
3400 Spruce Street 7103 Founders Pavilion
Philadelphia, PA 19104
Office: 215-662-6575
Fax: 215-662-7529
Education
B.S (Chemical Biology)
Stevens Institute of Technology, 1993.
Ph.D (Experimental Pathology/ Immunology)
UMDNJ - Graduate School of Biomedical Sciences, 1999.
M.D. (Medical Doctor)
UMDNJ- New Jersey Medical School, 1999.
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Description of Research Expertise

Research in my laboratory is focused on T cell biology and applications of genetically-engineered T cells to the treatment of disease.

Active research projects in my laboratory include:

1) Developing chimeric antigen receptors (CARs) and other engineering approaches for enhancing the function and improved safety of adoptive T cell therapy.

2) Developing and applying synthetic immunoreceptors to the treatment of immune-mediated disease.

3) Exploring the role of co-stimulatory signals in directing T cell metabolism and the way this metabolism affects T cell function within tumors.

Description of Clinical Expertise

Clinical Laboratory Toxicology, Therapeutic Drug Monitoring, Clinical Chemistry, Blood Banking/Transfusion Medicine, Therapeutic Apheresis

Selected Publications

Bhoj VG, Kaminski M, Zhao H, Jackson K, Wang W, Liu C, Montgomery RA, Ali N, Mangiola M, Spitzer TR, Safa K, Pattanayak V, Taj R, Chiu J, Bui TM, Sonnenberg EM, Markmann JF, Milone MC, June CH, Siegel DL, Fraietta JA, Gonzalez V, Locci M, Palmer M, Monos D, Hwang WT, Sledge T, Bridges ND, Goldstein JS, Odim J, Sweet SC, Besharatian BD, Hussain SM, Brown NK, Kamoun M, Garfall AL, Naji A.: Kidney Transplantation in Two Highly Sensitized Candidates after CAR T-Cell Therapy. N Engl J Med 394: 2117-2125, Jun 2026.

Frazee CS, Chen S, Berry CT, Lee CS, Banciella RA, Ngo L, Shon D, Herman PJ, Fischman JS, Leff CL, Chen A, Kuo Y, Shestov AA, Kelly AR, Valentic B, Milone MC, O'Connor RS, Ellebrecht CT.: Fate induction through asymmetric T cell division is modulated by chimeric antigen receptor costimulatory domains. Nat Immunol Jun 2026.

Gu M, Read KA, Bhardwaj V, Carvalho EJ, Nardo D, Shayne JC, Shukla D, Liu W, Siegel DL, Sheppard NC, Milone MC, Cohen AD, Garfall AL, Riley JL.: Rab5 improves CAR T cell efficacy via reducing fratricide and maintaining surface CAR levels. J Exp Med 223: e20252564, Jun 2026.

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.

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.

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.

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.

Zhang Q, Wu Y, Yang J, Zhou K, Manoharan ENEA, Wentz T, Su L, Yu A, Wang HY, Bruhn L, Steinfeld I, Gonzalez N, Song EZ, Zhang Y, Hresko ME, Ryan DE, Engel NW, Nunez-Cruz S, June CH, Garcia KC, Milone MC.: Viral vector-free generation of orthogonal IL-2-responsive CAR T cells through gene editing of IL-2 and its receptor. Blood Immunol Cell Ther 2025.

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.

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.

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Last updated: 08/11/2026
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