Frederick Locke, MD
Researcher

Frederick Locke, MD

Academic Rank: Associate Member

Overview

Dr. Locke is focused on developing strategies to promote T cell responses against tumor associated antigens for patients with cancer.

Discipline

    • Blood and Marrow Transplant and Cellular Immunotherapy
    • Immunology
    • Immunology

Education & Training

    • Wayne State University, MD
    • Wayne State University/Detroit Medical Center , Resident/Chief Resident - Internal Medicine
    • University of Chicago Medical Center, Fellow - Hematology/Oncology
Research

Dr. Locke is a physician and translational investigator specializing in the treatment of lymphoma and multiple myeloma in the Department of Blood and Marrow Transplantation at Moffitt. He is focused on developing strategies to promote T cell responses against tumor associated antigens for patients with these diseases and is the principal investigator for multiple cellular immunotherapy trials. He is a lead investigator for two national multi-center phase I/II studies treating aggressive lymphoma patients with anti-CD19 CAR T cells and the site PI of a randomized multi-center trial testing infusion of tumor (marrow) infiltrating lymphocytes for multiple myeloma. Dr. Locke’s translational research evaluates T cell responses against tumor associated antigens and neoantigens in myeloma patients. His findings justified a trial evaluating the biological activity of a unique Moffitt-created survivin dendritic cell vaccine using a novel schedule in conjunction with autologous transplant. Dr. Locke is the Chair of the Moffitt Cellular Therapy Advisory Committee and the Chair of the Moffitt Immunotherapy Working Group. In addition he is the Service Chief of the Moffitt Immune and Cellular Therapy (ICE-T) service, which was created to provide specialized clinical care for patients undergoing cellular immunotherapy treatments.

Publications

  • Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N, Westin J, Gulbis AM, Loghin ME, de Groot JF, Adkins S, Davis SE, Rezvani K, Hwu P, Shpall EJ. Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2017 Sep. Pubmedid: 28925994.
  • Chavez J, Locke FL. A Possible Cure for Refractory DLBCL: CARs Are Headed in the Right Direction. Mol Ther. 2017 Oct;25(10):2241-2243. Pubmedid: 28941574. Pmcid: PMC5628929.
  • Kharfan-Dabaja MA, Kumar A, Stingo FE, Khimani F, Hussaini M, Ayala E, Nishihori T, Shah B, Locke FL, Pinilla-Ibarz J, Chavez JC. Allogeneic Hematopoietic Cell Transplantation for Richter Syndrome: A Single-Center Experience. Clin Lymphoma Myeloma Leuk. 2017 Oct. Pubmedid: 29126867.
  • Murthy HS, Sheets K, Kumar A, Nishihori T, Mina A, Chavez JC, Ayala E, Field T, Mathews J, Locke F, Perez L, Betts BC, Khimani F, Miladinovic B, Tsalatsanis A, Ochoa-Bayona JL, Alsina M, Fernandez H, Pidala J, Anasetti C, Kharfan-Dabaja MA. Hypoalbuminemia at Day +90 Is Associated with Inferior Nonrelapse Mortality and Overall Survival in Allogeneic Hematopoietic Cell Transplantation Recipients: A Confirmatory Study. Biol Blood Marrow Tr. 2017 Oct. Pubmedid: 29032266.
  • Betts BC, Pidala J, Kim J, Mishra A, Nishihori T, Perez L, Ochoa-Bayona JL, Khimani F, Walton K, Bookout R, Nieder M, Khaira DK, Davila M, Alsina M, Field T, Ayala E, Locke FL, Riches M, Kharfan-Dabaja M, Fernandez H, Anasetti C. IL-2 promotes early Treg reconstitution after allogeneic hematopoietic cell transplantation. Haematologica. 2017 May;102(5):948-957. Pubmedid: 28104702. Pmcid: PMC5477614.
  • Locke FL, Pidala J, Storer B, Martin PJ, Pulsipher MA, Chauncey TR, Jacobsen N, Kröger N, Walker I, Light S, Shaw BE, Beato F, Laport GG, Nademanee A, Keating A, Socie G, Anasetti C. CD25 Blockade Delays Regulatory T Cell Reconstitution and Does Not Prevent Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Tr. 2017 Mar;23(3):405-411. Pubmedid: 28007665.
  • Locke FL, Davila ML. Regulatory challenges and considerations for the clinical application of CAR-T cell anti-cancer therapy. Expert Opin Biol Ther. 2017 Jun;17(6):659-661. Pubmedid: 28454503.
  • Locke FL, Anasetti C. Transplanters drive CARs to the clinic by brewing ICE-T: the Moffitt roadmap. J Immunother Cancer. 2017 Jul;5:59. Pubmedid: 28725432. Pmcid: PMC5514522.
  • Khimani F, Kim J, Chen L, Dean E, Rizk V, Betts B, Nishihori T, Locke F, Mishra A, Perez L, Ayala E, Kharfan-Dabaja M, Nieder M, Fernandez H, Anasetti C, Pidala J. Predictors of overall survival among patients treated with sirolimus/tacrolimus vs methotrexate/tacrolimus for GvHD prevention. Bone Marrow Transplant. 2017 Jul;52(7):1003-1009. Pubmedid: 28368376.
  • Locke FL, Anasetti C. Transplanters drive CARs to the clinic by brewing ICE-T: the Moffitt roadmap. J Immunother Cancer. 2017 Jul;5(1):59. Pubmedid: 28716155. Pmcid: PMC5514522.
  • Hampras SS, Locke FL, Chavez JC, Patel NS, Giuliano AR, Miller K, Gheit T, Tommasino M, Rollison DE. Prevalence of cutaneous viral infections in incident cutaneous squamous cell carcinoma detected among chronic lymphocytic leukemia and hematopoietic stem cell transplant patients. Leuk Lymphoma. 2017 Jul;1-7. Pubmedid: 28679298.
  • Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma. Mol Ther. 2017 Jan;25(1):285-295. Pubmedid: 28129122. Pmcid: PMC5363293.
  • Locke FL. Highlights in Aggressive Non-Hodgkin Lymphoma From the 2017 American Society of Clinical Oncology Annual Meeting: Commentary. Clin Adv Hematol Oncol. 2017 Aug;15 Suppl 8(8):16-19. Pubmedid: 28837125.
  • Tees MT, Betts B, Hillgruber R, Ayala E, Field T, Kharfan-Dabaja MA, Locke F, Mishra A, Nishihori T, Ochoa-Bayona JL, Perez L, Pidala J, Anasetti C, Fernandez H, Riches ML. New sources for argument: do HLA-C and HLA disparity in adult double umbilical cord blood transplants predict outcomes?. Bone Marrow Transplant. 2016 Sep;51(9):1256-1258. Pubmedid: 27088383.
  • Locke FL, Menges M, Nishihori T, Nwoga C, Alsina M, Anasetti C. Boosting humoral and cellular immunity to pneumococcus by vaccination before and just after autologous transplant for myeloma. Bone Marrow Transplant. 2016 Feb;51:291-294. Pubmedid: 26457911.
  • Khimani F, Jeong DK, Miladinovic B, Nishihori T, Ayala E, Locke F, Mishra A, Chavez J, Shah B, Gage K, Kharfan-Dabaja MA. Nonfluorodeoxyglucose-Avid Persistent Splenomegaly at Time of Transplantation Delays Neutrophil and Platelets Engraftment without Affecting Survival in Patients with Lymphomas Undergoing Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Tr. 2016 Dec;22(12):2201-2207. Pubmedid: 27660169.
  • Chavez JC, Piris-Villaespesa M, Dalia S, Powers J, Turba E, Nodzon L, Komrokji R, Sokol L, Locke FL, Lancet J, Sotomayor EM, Kharfan-Dabaja MA, Pinilla-Ibarz J. Results of a phase II study of lenalidomide and rituximab for refractory/relapsed chronic lymphocytic leukemia. Leuk Res. 2016 Aug;47:78-83. Pubmedid: 27285853.
  • Nelson R, Shapiro JF, Perkins JB, Kim J, Nishihori T, Pidala J, Ayala E, Locke FL, Field T, Mishra A, Riches M, Betts B, Perez L, Yue B, Ochoa-Bayona JL, Alsina M, Fernandez H, Anasetti C, Kharfan-Dabaja MA. Sirolimus, tacrolimus and antithymocyte globulin as GVHD prophylaxis in HLA-mismatched unrelated donor hematopoietic cell transplantation: a single institution experience. Bone Marrow Transplant. 2015 Nov;50(11):1487-1489. Pubmedid: 26301969. Pmcid: PMC4863975.
  • Locke FL, Menges M, Veerapathran A, Coppola D, Gabrilovich D, Anasetti C. Survivin-specific CD4+ T cells are decreased in patients with survivin-positive myeloma. J Immunother Cancer. 2015 May;3:20. Pubmedid: 25992291. Pmcid: PMC4437443.
  • Ayala E, Figueroa J, Perkins J, Kim J, Yue B, Riches M, Nishihori T, Locke F, Anasetti C, Kharfan-Dabaja MA. Myeloablative intravenous pharmacokinetically targeted busulfan plus fludarabine as conditioning for allogeneic hematopoietic cell transplantation in patients with non-hodgkin lymphoma. Clin Lymphoma Myeloma Leuk. 2015 Jun;15(6):335-340. Pubmedid: 25659459.
  • Pidala J, Kim J, Betts BC, Alsina M, Ayala E, Fernandez HF, Field T, Kharfan-Dabaja MA, Locke FL, Mishra A, Nishihori T, Ochoa-Bayona L, Perez L, Riches M, Anasetti C. Ofatumumab in combination with glucocorticoids for primary therapy of chronic graft-versus-host disease: phase I trial results. Biol Blood Marrow Tr. 2015 Jun;21(6):1074-1082. Pubmedid: 25805300.
  • Zimmerman A, Locke FL, Emole J, Rosa M, Horna P, Hoover S, Dayicioglu D. Recurrent Systemic Anaplastic Lymphoma Kinase-Negative Anaplastic Large Cell Lymphoma Presenting as a Breast Implant-Associated Lesion. Cancer Control. 2015 Jul;22(3):369-373. Pubmedid: 26351895.
  • Pidala J, Kim J, Alsina M, Ayala E, Betts BC, Fernandez HF, Field T, Jim H, Kharfan-Dabaja MA, Locke FL, Mishra A, Nishihori T, Ochoa-Bayona L, Perez L, Riches M, Anasetti C. Prolonged sirolimus administration after allogeneic hematopoietic cell transplantation is associated with decreased risk for moderate-severe chronic graft-versus-host disease. Haematologica. 2015 Jul;100(7):970-977. Pubmedid: 25840599. Pmcid: PMC4486232.
  • Locke FL, Rollison DE, Sondak VK. Merkel cell carcinoma and immunosuppression: what we still need to know. J Natl Cancer Inst. 2015 Feb;107(2). Pubmedid: 25575646.
  • Emole JN, Locke FL, Pinilla-Ibarz J. An update on current and prospective immunotherapies for chronic lymphocytic leukemia. Immunotherapy. 2015 Apr;7(4):455-466. Pubmedid: 25917633.
  • Chavez JC, Kharfan-Dabaja MA, Kim J, Yue B, Dalia S, Pinilla-Ibarz J, Anasetti C, Locke FL. Genomic aberrations deletion 11q and deletion 17p independently predict for worse progression-free and overall survival after allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia. Leuk Res. 2014 Oct;38(10):1165-1172. Pubmedid: 24889511. Pmcid: PMC4625795.
  • Kunter G, Perkins JB, Pidala J, Nishihori T, Kharfan-Dabaja MA, Field T, Fernandez H, Perez L, Locke F, Ayala E, Tomblyn M, Ochoa-Bayona JL, Betts B, Nieder M, Anasetti C. Pharmacokinetically-targeted BU and fludarabine as conditioning before allogeneic hematopoietic cell transplantation for adults with ALL in first remission. Bone Marrow Transplant. 2014 Jan;49(1):11-16. Pubmedid: 23995098.
  • Locke FL, Nishihori T, Alsina M, Kharfan-Dabaja MA. Immunotherapy strategies for multiple myeloma: the present and the future. Immunotherapy. 2013 Sep;5(9):1005-1020. Pubmedid: 23998734. Pmcid: PMC4905571.
  • Pidala J, Kim J, Schell M, Lee SJ, Hillgruber R, Nye V, Ayala E, Alsina M, Betts B, Bookout R, Fernandez HF, Field T, Locke FL, Nishihori T, Ochoa JL, Perez L, Perkins J, Shapiro J, Tate C, Tomblyn M, Anasetti C. Race/ethnicity affects the probability of finding an HLA-A, -B, -C and -DRB1 allele-matched unrelated donor and likelihood of subsequent transplant utilization. Bone Marrow Transplant. 2013 Mar;48(3):346-350. Pubmedid: 22863723. Pmcid: PMC4500122.
  • Kharfan-Dabaja MA, Anasetti C, Fernandez HF, Perkins J, Ochoa-Bayona JL, Pidala J, Perez LE, Ayala E, Field T, Alsina M, Nishihori T, Locke F, Pinilla-Ibarz J, Tomblyn M. Phase II study of CD4+-guided pentostatin lymphodepletion and pharmacokinetically targeted busulfan as conditioning for hematopoietic cell allografting. Biol Blood Marrow Tr. 2013 Jul;19(7):1087-1093. Pubmedid: 23632090. Pmcid: PMC4667782.
  • Locke FL, Zha YY, Zheng Y, Driessens G, Gajewski TF. Conditional deletion of PTEN in peripheral T cells augments TCR-mediated activation but does not abrogate CD28 dependency or prevent anergy induction. J Immunol. 2013 Aug;191(4):1677-1685. Pubmedid: 23851688. Pmcid: PMC3759681.
  • Zheng Y, Zha Y, Driessens G, Locke F, Gajewski TF. Transcriptional regulator early growth response gene 2 (Egr2) is required for T cell anergy in vitro and in vivo. J Exp Med. 2012 Nov;209(12):2157-2163. Pubmedid: 23129747. Pmcid: PMC3501351.
  • Locke FL, Morgan GJ. What is the evidence for the use of bisphosphonate therapy in newly diagnosed multiple myeloma patients lacking bone disease?. Hematology Am Soc Hematol Educ Program. 2012 Dec;2012:350-353. Pubmedid: 23233603.
  • Pidala J, Kim J, Jim H, Kharfan-Dabaja MA, Nishihori T, Fernandez HF, Tomblyn M, Perez L, Perkins J, Xu M, Janssen WE, Veerapathran A, Betts BC, Locke FL, Ayala E, Field T, Ochoa L, Alsina M, Anasetti C. A randomized phase II study to evaluate tacrolimus in combination with sirolimus or methotrexate after allogeneic hematopoietic cell transplantation. Haematologica. 2012 Dec;97(12):1882-1889. Pubmedid: 22689677. Pmcid: PMC3590095.
  • Pidala J, Tomblyn M, Nishihori T, Field T, Ayala E, Perkins J, Fernandez H, Locke F, Perez L, Ochoa JL, Alsina M, Anasetti C. Sirolimus demonstrates activity in the primary therapy of acute graft-versus-host disease without systemic glucocorticoids. Haematologica. 2011 Sep;96(9):1351-1356. Pubmedid: 21565902. Pmcid: PMC3166106.
  • Pidala J, Tomblyn M, Nishihori T, Ayala E, Field T, Fernandez H, Perez L, Locke F, Alsina M, Ochoa JL, Perkins J, Tate C, Shapiro J, Conwell M, Bookout R, Anasetti C. ATG prevents severe acute graft-versus-host disease in mismatched unrelated donor hematopoietic cell transplantation. Biol Blood Marrow Tr. 2011 Aug;17(8):1237-1244. Pubmedid: 21215811.
  • Locke F, Clark JI, Gajewski TF. A phase II study of oxaliplatin, docetaxel, and GM-CSF in patients with previously treated advanced melanoma. Cancer Chemother Pharmacol. 2010 Feb;65(3):509-514. Pubmedid: 19597729.
  • Locke FL, Artz A, Rich E, Zhang Y, van Besien K, Stock W. Feasibility of clofarabine cytoreduction before allogeneic transplant conditioning for refractory AML. Bone Marrow Transplant. 2010 Dec;45(12):1692-1698. Pubmedid: 20208570.
  • Zha Y, Shah R, Locke F, Wong A, Gajewski TF. Use of Cre-adenovirus and CAR transgenic mice for efficient deletion of genes in post-thymic T cells. J Immunol Methods. 2008 Feb;331(1-2):94-102. Pubmedid: 18177887. Pmcid: PMC3278801.
  • Mattison RJ, Ostler KR, Locke FL, Godley LA. Implications of FLT3 mutations in the therapy of acute myeloid leukemia. Rev Recent Clin Trials. 2007 May;2(2):135-141. Pubmedid: 18473998.