Update Your ProfileAcademic Title:
Associate Professor
Primary Appointment:
Medicine
Additional Title:
Medical Director, Cell Therapy & Graft Engineering Laboratories
Email:
Location:
North Hospital, N9E12
Phone (Primary):
410-328-1230
Fax:
410-328-1975
Education and Training
BA: Carroll College (Helena, MT), History and Political Science
MA: American University School of International Service (Washington, DC), International Development. Thesis: Socioeconomic Determinants of HIV Infection in Women in Africa
MD: University of Washington School of Medicine (Seattle, WA)
Internship, Internal Medicine, Duke University Medical Center
Internal Medicine, Duke University Medical Center
Clinical Fellowship, Medical Oncology, Duke University Medical Center
Clinical Fellowship, Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID)
Research Fellowship, Medical Oncology and Infectious Disease, NCI/Experimental Immunology Branch, Transplantation Immunology. Mentor: Ronald Gress: regulation of T-cell homeostasis in murine systems
Biosketch
My research focuses on clinical and translational development and characterization of cellular immunotherapies for cancer. With comprehensive clinical training in medical oncology and host-defense oriented infectious diseases, as well as laboratory postdoctoral training in basic experimental transplantation and immunology, I have unique translational research expertise in cancer immunotherapy. While at the National Cancer Institute (NCI), I explored ways of augmenting the allogeneic immune response after stem cell transplantation (SCT) to treat cancer relapse. This led to the identification of donor-derived tumor infiltrating lymphocytes and their ex-vivo expansion and cell therapy for tumor progression after SCT (Hardy, 2012), and piloting radiation-enhanced cell therapy to boost tumor immune responses in vivo. Collaborations within the NCI investigated allograft engineering (Hardy, 2011; Fowler, 2013), and led to the establishment of chimeric antigen-receptor (CAR) T-cell therapies targeting CD19 and BCMA for B-cell malignancies and multiple myeloma, respectively (Kochenderfer, 2013). In my current position, I directly oversee key aspects of cell therapy at the University of Maryland Greenebaum Comprehensive Center (target-cell collection by apheresis; cell processing; patient administration). I bring my translational immunotherapy expertise to partnerships with scientific investigators in academics and industry to develop cell processing innovations and identify therapeutic targets for emerging engineered T-cell therapeutics. For example, I am collaborating with scientists from the University of Maryland Center for Stem Cell Biology & Regenerative Medicine and physicists & engineers at Princeton University on scale-up and commercialization of a novel microfluidics technology which permits rapid and gentle target cell enrichment, moving this diagnostics-scale technology to clinical scale to improve manufacturing of cell therapy. My active clinical research encompasses all phases of cell therapy trials with investigators across the campus and around the world, including CD19 CAR-T cells, genetically modified T cells expressing enhanced T cell receptors specific for tumor associated antigens and placenta-derived stromal cells for bone marrow regeneration.
Research/Clinical Keywords
Hematopoietic Stem Cell Transplantation, Blood and Marrow Transplantation (BMT)
Highlighted Publications
Kochenderfer JN, Dudley ME, Carpenter RO, Kassim SH, Rose JJ, Telford WG, Hakim FT, Halverson DC, Fowler DH, Hardy NM, Mato AR, Hickstein DD, Gea-Banacloche JC, Pavletic SZ, Sportes C, Maric I, Feldman SA, Hansen BG, Wilder JS, Blacklock-Schuver B, Jena B, Bishop MR, Gress RE, Rosenberg SA. Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood. 2013 Dec 12;122(25):4129-39. PubMed PMID: 24055823; PubMed Central PMCID: PMC3862276.
Fowler DH, Mossoba ME, Steinberg SM, Halverson DC, Stroncek D, Khuu HM, Hakim FT, Castiello L, Sabatino M, Leitman SF, Mariotti J, Gea-Banacloche JC, Sportes C, Hardy NM, Hickstein DD, Pavletic SZ, Rowley S, Goy A, Donato M, Korngold R, Pecora A, Levine BL, June CH, Gress RE, Bishop MR. Phase 2 clinical trial of rapamycin-resistant donor CD4+ Th2/Th1 (T-Rapa) cells after low-intensity allogeneic hematopoietic cell transplantation. Blood. 2013 Apr 11;121(15):2864-74. PubMed PMID: 23426943; PubMed Central PMCID: PMC3624934.
Hardy NM, Fellowes V, Rose JJ, Odom J, Pittaluga S, Steinberg SM, Blacklock-Schuver B, Avila DN, Memon S, Kurlander RJ, Khuu HM, Stetler-Stevenson M, Mena E, Dwyer AJ, Levine BL, June CH, Reshef R, Vonderheide RH, Gress RE, Fowler DH, Hakim FT, Bishop MR. Costimulated tumor-infiltrating lymphocytes are a feasible and safe alternative donor cell therapy for relapse after allogeneic stem cell transplantation. Blood. 2012 Mar 22;119(12):2956-9. PubMed PMID: 22289893; PubMed Central PMCID: PMC3327466.
Hardy NM, Mossoba ME, Steinberg SM, Fellowes V, Yan XY, Hakim FT, Babb RR, Avila D, Gea-Banacloche J, Sportès C, Levine BL, June CH, Khuu HM, Carpenter AE, Krumlauf MC, Dwyer AJ, Gress RE, Fowler DH, Bishop MR. Phase I trial of adoptive cell transfer with mixed-profile type-I/type-II allogeneic T cells for metastatic breast cancer. Clin Cancer Res. 2011 Nov 1;17(21):6878-87. PubMed PMID: 21948234; PubMed Central PMCID: PMC3206984.
Research Interests
Donor lymphocyte infusion (DLI) is an established therapeutic option for patients with disease relapse, incomplete donor engraftment and/or poor immune reconstitution post-transplant but often results in GvHD and are not available for many patients. My research identified that after allogeneic stem cell transplantation, tumor-infiltrating lymphocytes are of donor origin, can be expanded to clinically relevant numbers ex vivo, and infusion of tumor-derived donor lymphocytes is not associated with GvHD. Tumor-derived donor lymphocytes may be a therapeutic option for patients without other sources of donor lymphocyte infusion.
- Hardy NM, Fellowes V, Rose JJ, Odom J, Pittaluga S, Steinberg SM, Blacklock-Schuver B, Avila DN, Memon S, Kurlander RJ, Khuu HM, Stetler-Stevenson M, Mena E, Dwyer AJ, Levine BL, June CH, Reshef R, Vonderheide RH, Gress RE, Fowler DH, Hakim FT, Bishop MR. Costimulated tumor-infiltrating lymphocytes are a feasible and safe alternative donor cell therapy for relapse after allogeneic stem cell transplantation. Blood. 2012 Mar 22;119(12):2956-9. PubMed PMID: 22289893; PubMed Central PMCID: PMC3327466.
Allogeneic CD8 T cells mediate breast cancer regression via a graft-vs. tumor (GvT) effect, and the effective CD8 T-cell dose, relative to residual host CD8 T-cells, is closely linked to establishment of complete donor T cell chimerism and development of graft-vs.-host disease (GvHD). The importance of CD8 T-cell dose in engraftment and GVHD-associated GvT has broader implications for treating mixed chimerism after allogeneic stem cell transplantation.
- Hardy NM, Mossoba ME, Steinberg SM, Fellowes V, Yan XY, Hakim FT, Babb RR, Avila D, Gea-Banacloche J, Sportès C, Levine BL, June CH, Khuu HM, Carpenter AE, Krumlauf MC, Dwyer AJ, Gress RE, Fowler DH, Bishop MR. Phase I trial of adoptive cell transfer with mixed-profile type-I/type-II allogeneic T cells for metastatic breast cancer. Clin Cancer Res. 2011 Nov 1;17(21):6878-87. PubMed PMID: 21948234; PubMed Central PMCID: PMC3206984.
- Hardy NM, Hakim F, Steinberg SM, Krumlauf M, Cvitkovic R, Babb R, Odom J, Fowler DH, Gress RE, Bishop MR. Host T cells affect donor T cell engraftment and graft-versus-host disease after reduced-intensity hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2007 Sep;13(9):1022-30. PubMed PMID: 17697964; PubMed Central PMCID: PMC2699412.
- Bishop MR, Steinberg SM, Gress RE, Hardy NM, Marchigiani D, Kasten-Sportes C, Dean R, Pavletic SZ, Gea-Banacloche J, Castro K, Hakim F, Krumlauf M, Read EJ, Carter C, Leitman SF, Fowler DH. Targeted pretransplant host lymphocyte depletion prior to T-cell depleted reduced-intensity allogeneic stem cell transplantation. Br J Haematol. 2004 Sep;126(6):837-43. PubMed PMID: 15352988.
Native anti-tumor immune responses may be ineffective in controlling cancer due to immune tolerance, cell exhaustion or and/anergy. Radiation promotes immune activation of novel immune effector cell populations through damage to cancer cells and disruption of the tumor microenvironment. Systemic toxicity of local irradiation often includes off-target bone marrow suppression. My research has shown that targeted, hypofractionated radiation can be safely administered to augment donor lymphocyte infusion in previously transplanted patients who develop cancer relapse and that radiation can enhance systemic (“abscopal”) antitumor immune responses.
- Hardy N, Citrin D, Hakim F, Avila D, Blacklock-Schuver B, Cotton S, Cho M, Fowler D, Gea-Banacloche J, Holtzman N, Kurdziel K, Memon S, Pavletic S, Pittaluga S, Rose J, Sportes C, Wilder J, Gress R, Bishop M. Pilot Study of Radiation-Targeted Donor Lymphocyte Infusion for Cancer Progression after Allogeneic Hematopoietic Stem Cell Transplantation. Blood. 126(23):1962-1962.
Awards and Affiliations
1991 MA with Honors, American University School of International Service
1992 Teaching Assistantship, University of Washington School of Medicine
1995 MD with Honors, University of Washington School of Medicine