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1. A phase 1/2 clinical trial of invariant natural killer T cell therapy in moderate-severe acute respiratory distress syndrome

Author

Hammond, Terese C., Purbhoo, Marco A., Kadel, Sapana, Ritz, Jerome, Nikiforow, Sarah, Daley, Heather, Shaw, Kit, van Besien, Koen, Gomez-Arteaga, Alexandra, Stevens, Don, Ortuzar, Waldo, Michelet, Xavier, Smith, Rachel, Moskowitz, Darrian, Masakayan, Reed, Yigit, Burcu, Boi, Shannon, Soh, Kah Teong, Chamberland, John, Song, Xin, Qin, Yu, Mishchenko, Ilya, Kirby, Maurice, Nasonenko, Valeriia, Buffa, Alexa, Buell, Jennifer S., Chand, Dhan, van Dijk, Marc, Stebbing, Justin, and Exley, Mark A.

Published
2024
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3. Baseline immune state and T-cell clonal kinetics are associated with durable response to CAR-T therapy in large B-cell lymphoma

Author

Maurer, Katie, Grabski, Isabella N., Houot, Roch, Gohil, Satyen H., Miura, Shogo, Redd, Robert, Lyu, Haoxiang, Lu, Wesley, Arihara, Yohei, Budka, Justin, McDonough, Mikaela, Ansuinelli, Michela, Reynolds, Carol, Jacene, Heather, Li, Shuqiang, Livak, Kenneth J., Ritz, Jerome, Miles, Brodie, Mattie, Mike, Neuberg, Donna S., Irizarry, Rafael A., Armand, Philippe, Wu, Catherine J., and Jacobson, Caron

Published
2024
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4. Phase 1 study of CAR-37 T cells in patients with relapsed or refractory CD37+ lymphoid malignancies

Author

Frigault, Matthew J., Graham, Charlotte E., Berger, Trisha R., Ritchey, Julie, Horick, Nora K., El-Jawahri, Areej, Scarfò, Irene, Schmidts, Andrea, Haradhvala, Nicholas J., Wehrli, Marc, Lee, Won-Ho, Parker, Aiyana L., Wiggin, Hadley R., Bouffard, Amanda, Dey, Aonkon, Leick, Mark B., Katsis, Katelin, Elder, Eva L., Dolaher, Maria A., Cook, Daniella T., Chekmasova, Alena A., Huang, Lu, Nikiforow, Sarah, Daley, Heather, Ritz, Jerome, Armant, Myriam, Preffer, Fred, DiPersio, John F., Nardi, Valentina, Chen, Yi-Bin, Gallagher, Kathleen M. E., and Maus, Marcela V.

Published
2024
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5. Active infection at the time of CD34+ selected stem cell boost is associated with treatment failure and poor overall survival

Author

Shapiro, Roman M., Kim, Haesook T., Dulery, Remy, Liney, Deborah, Garrity, Heather M., Panaro, Kevin, Au, Chloe, Gervais, Casey, Little, Jessica S., Ho, Vincent T., Cutler, Corey S., Koreth, John, Gooptu, Mahasweta, Antin, Joseph H., Kelkar, Amar H., Romee, Rizwan, Wu, Catherine J., Ritz, Jerome, Soiffer, Robert J., and Nikiforow, Sarah

Published
2024
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6. Liquid biopsy epigenomic profiling for cancer subtyping

Author

Baca, Sylvan C., Seo, Ji-Heui, Davidsohn, Matthew P., Fortunato, Brad, Semaan, Karl, Sotudian, Shahabbedin, Lakshminarayanan, Gitanjali, Diossy, Miklos, Qiu, Xintao, El Zarif, Talal, Savignano, Hunter, Canniff, John, Madueke, Ikenna, Saliby, Renee Maria, Zhang, Ziwei, Li, Rong, Jiang, Yijia, Taing, Len, Awad, Mark, Chau, Cindy H., DeCaprio, James A., Figg, William D., Greten, Tim F., Hata, Aaron N., Hodi, F. Stephen, Hughes, Melissa E., Ligon, Keith L., Lin, Nancy, Ng, Kimmie, Oser, Matthew G., Meador, Catherine, Parsons, Heather A., Pomerantz, Mark M., Rajan, Arun, Ritz, Jerome, Thakuria, Manisha, Tolaney, Sara M., Wen, Patrick Y., Long, Henry, Berchuck, Jacob E., Szallasi, Zoltan, Choueiri, Toni K., and Freedman, Matthew L.

Published
2023
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9. Prophylactic maintenance with venetoclax/azacitidine after reduced-intensity conditioning allogeneic transplant for high-risk MDS and AML

Author

Garcia, Jacqueline S., Kim, Haesook T., Murdock, H. Moses, Ansuinelli, Michela, Brock, Jennifer, Cutler, Corey S., Gooptu, Mahasweta, Ho, Vincent T., Koreth, John, Nikiforow, Sarah, Romee, Rizwan, Shapiro, Roman, DeAngelo, Daniel J., Stone, Richard M., Bat-Erdene, Denbaa, Ryan, Jeremy, Contreras, Manuel E., Fell, Geoffrey, Letai, Anthony, Ritz, Jerome, Lindsley, R. Coleman, Soiffer, Robert J., and Antin, Joseph H.

Published
2024
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10. Author Correction: Liquid biopsy epigenomic profiling for cancer subtyping

Author

Baca, Sylvan C., Seo, Ji-Heui, Davidsohn, Matthew P., Fortunato, Brad, Semaan, Karl, Sotudian, Shahabbedin, Lakshminarayanan, Gitanjali, Diossy, Miklos, Qiu, Xintao, El Zarif, Talal, Savignano, Hunter, Canniff, John, Madueke, Ikenna, Saliby, Renee Maria, Zhang, Ziwei, Li, Rong, Jiang, Yijia, Taing, Len, Awad, Mark, Chau, Cindy H., DeCaprio, James A., Figg, William D., Greten, Tim F., Hata, Aaron N., Hodi, F. Stephen, Hughes, Melissa E., Ligon, Keith L., Lin, Nancy, Ng, Kimmie, Oser, Matthew G., Meador, Catherine, Parsons, Heather A., Pomerantz, Mark M., Rajan, Arun, Ritz, Jerome, Thakuria, Manisha, Tolaney, Sara M., Wen, Patrick Y., Long, Henry, Berchuck, Jacob E., Szallasi, Zoltan, Choueiri, Toni K., and Freedman, Matthew L.

Published
2024
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13. Distinct evolutionary paths in chronic lymphocytic leukemia during resistance to the graft-versus-leukemia effect

Author

Bachireddy, Pavan, Ennis, Christina, Nguyen, Vinhkhang N, Gohil, Satyen H, Clement, Kendell, Shukla, Sachet A, Forman, Juliet, Barkas, Nikolaos, Freeman, Samuel, Bavli, Natalie, Elagina, Liudmila, Leshchiner, Ignaty, Mohammad, Arman W, Mathewson, Nathan D, Keskin, Derin B, Rassenti, Laura Z, Kipps, Thomas J, Brown, Jennifer R, Getz, Gad, Ho, Vincent T, Gnirke, Andreas, Neuberg, Donna, Soiffer, Robert J, Ritz, Jerome, Alyea, Edwin P, Kharchenko, Peter V, and Wu, Catherine J

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Immunology, Orphan Drug, Stem Cell Research - Nonembryonic - Human, Regenerative Medicine, Cancer, Stem Cell Research, Human Genome, Hematology, Lymphoma, Clinical Research, Rare Diseases, Lymphatic Research, Transplantation, Genetics, Graft vs Host Disease, Graft vs Leukemia Effect, HLA Antigens, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Transplantation, Homologous, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract

Leukemic relapse remains a major barrier to successful allogeneic hematopoietic stem cell transplantation (allo-HSCT) for aggressive hematologic malignancies. The basis for relapse of advanced lymphoid malignancies remains incompletely understood and may involve escape from the graft-versus-leukemia (GvL) effect. We hypothesized that for patients with chronic lymphocytic leukemia (CLL) treated with allo-HSCT, leukemic cell-intrinsic features influence transplant outcomes by directing the evolutionary trajectories of CLL cells. Integrated genetic, transcriptomic, and epigenetic analyses of CLL cells from 10 patients revealed that the clinical kinetics of post-HSCT relapse are shaped by distinct molecular dynamics. Early relapses after allo-HSCT exhibited notable genetic stability; single CLL cell transcriptional analysis demonstrated a cellular heterogeneity that was static over time. In contrast, CLL cells relapsing late after allo-HSCT displayed notable genetic evolution and evidence of neoantigen depletion, consistent with marked single-cell transcriptional shifts that were unique to each patient. We observed a greater rate of epigenetic change for late relapses not seen in early relapses or relapses after chemotherapy alone, suggesting that the selection pressures of the GvL bottleneck are unlike those imposed by chemotherapy. No selective advantage for human leukocyte antigen (HLA) loss was observed, even when present in pretransplant subpopulations. Gain of stem cell modules was a common signature associated with leukemia relapse regardless of posttransplant relapse kinetics. These data elucidate the biological pathways that underlie GvL resistance and posttransplant relapse.

Published
2020

14. Personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson’s Disease

Author

Schweitzer, Jeffrey S, Song, Bin, Herrington, Todd M, Park, Tae-Yoon, Lee, Nayeon, Ko, Sanghyeok, Jeon, Jeha, Cha, Young, Kim, Kyungsang, Li, Quanzheng, Henchcliffe, Claire, Kaplitt, Michael, Neff, Carolyn, Rapalino, Otto, Seo, Hyemyung, Lee, In-Hee, Kim, Jisun, Kim, Taewoo, Petsko, Gregory A, Ritz, Jerome, Cohen, Bruce M, Kong, Sek-Won, Leblanc, Pierre, Carter, Bob S, and Kim, Kwang-Soo

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Neurodegenerative, Transplantation, Regenerative Medicine, Stem Cell Research - Induced Pluripotent Stem Cell, Clinical Research, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research, Parkinson's Disease, Brain Disorders, Neurosciences, Neurological, Good Health and Well Being, Aged, Animals, Basal Ganglia, Cell Differentiation, Disease Models, Animal, Dopaminergic Neurons, Follow-Up Studies, Humans, Induced Pluripotent Stem Cells, Male, Mice, Mice, SCID, Parkinson Disease, Pars Compacta, Positron-Emission Tomography, Putamen, Tomography, X-Ray Computed, Transplantation, Autologous, Transplantation, Homologous, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

We report the implantation of patient-derived midbrain dopaminergic progenitor cells, differentiated in vitro from autologous induced pluripotent stem cells (iPSCs), in a patient with idiopathic Parkinson's disease. The patient-specific progenitor cells were produced under Good Manufacturing Practice conditions and characterized as having the phenotypic properties of substantia nigra pars compacta neurons; testing in a humanized mouse model (involving peripheral-blood mononuclear cells) indicated an absence of immunogenicity to these cells. The cells were implanted into the putamen (left hemisphere followed by right hemisphere, 6 months apart) of a patient with Parkinson's disease, without the need for immunosuppression. Positron-emission tomography with the use of fluorine-18-L-dihydroxyphenylalanine suggested graft survival. Clinical measures of symptoms of Parkinson's disease after surgery stabilized or improved at 18 to 24 months after implantation. (Funded by the National Institutes of Health and others.).

Published
2020

18. Low-Dose Interleukin 2 for the Treatment of Moderate to Severe Ulcerative Colitis

Author

Hamilton, Matthew, Barends, Jared, Carrellas, Madeline, Freer, Katherine, Gringauz, Jordan, Green, Julia, Herwood, Noah, Hurtado, Jonathan, Kelly, Ryan, Mitri, Jennifer, Rourke, Caroline, Saccocia, Gwen, Whitcomb, Sydney, Liu, Enju, Klatzmann, David, de Silva, Punyanganie, Farraye, Frank A., Feuerstein, Joseph D., Moss, Alan, Shah, Samir A., Korzenik, Joshua R., Bousvaros, Athos, Koreth, John, Soiffer, Robert, Ritz, Jerome, Logvinenko, Tanya, Ananthakrishnan, Ashwin, Herfath, Hans, Allegretti, Jessica R., Mitsialis, Vanessa, Canavan, James B., and Snapper, Scott B.

Published
2023
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19. Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease

Author

Penter, Livius, Liu, Yang, Wolff, Jacquelyn O., Yang, Lin, Taing, Len, Jhaveri, Aashna, Southard, Jackson, Patel, Manishkumar, Cullen, Nicole M., Pfaff, Kathleen L., Cieri, Nicoletta, Oliveira, Giacomo, Kim-Schulze, Seunghee, Ranasinghe, Srinika, Leonard, Rebecca, Robertson, Taylor, Morgan, Elizabeth A., Chen, Helen X., Song, Minkyung H., Thurin, Magdalena, Li, Shuqiang, Rodig, Scott J., Cibulskis, Carrie, Gabriel, Stacey, Bachireddy, Pavan, Ritz, Jerome, Streicher, Howard, Neuberg, Donna S., Hodi, F. Stephen, Davids, Matthew S., Gnjatic, Sacha, Livak, Kenneth J., Altreuter, Jennifer, Michor, Franziska, Soiffer, Robert J., Garcia, Jacqueline S., and Wu, Catherine J.

Published
2023
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22. Targeting PI3Kδ function for amelioration of murine chronic graft-versus-host disease

Author

Paz, Katelyn, Flynn, Ryan, Du, Jing, Tannheimer, Stacey, Johnson, Amy J, Dong, Shuai, Stark, Anne-Katrien, Okkenhaug, Klaus, Panoskaltsis-Mortari, Angela, Sage, Peter T, Sharpe, Arlene H, Luznik, Leo, Ritz, Jerome, Soiffer, Robert J, Cutler, Corey S, Koreth, John, Antin, Joseph H, Miklos, David B, MacDonald, Kelli P, Hill, Geoffrey R, Maillard, Ivan, Serody, Jonathan S, Murphy, William J, Munn, David H, Feser, Colby, Zaiken, Michael, Vanhaesebroeck, Bart, Turka, Laurence A, Byrd, John C, and Blazar, Bruce R

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Immunology, Infectious Diseases, Rare Diseases, Transplantation, Prevention, Stem Cell Research, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Good Health and Well Being, Animals, B-Lymphocytes, Bone Marrow Transplantation, Bronchiolitis Obliterans, Chronic Disease, Class I Phosphatidylinositol 3-Kinases, Disease Models, Animal, Graft vs Host Disease, Humans, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, Mutant Strains, Phosphoinositide-3 Kinase Inhibitors, Scleroderma, Localized, T-Lymphocytes, Helper-Inducer, basic (laboratory) research, science, graft-versus-host disease, immunobiology, immunosuppressant - other, basic (laboratory) research/science, Medical and Health Sciences, Surgery, Clinical sciences
Abstract

Chronic graft-versus-host disease (cGVHD) is a leading cause of morbidity and mortality following allotransplant. Activated donor effector T cells can differentiate into pathogenic T helper (Th)-17 cells and germinal center (GC)-promoting T follicular helper (Tfh) cells, resulting in cGVHD. Phosphoinositide-3-kinase-δ (PI3Kδ), a lipid kinase, is critical for activated T cell survival, proliferation, differentiation, and metabolism. We demonstrate PI3Kδ activity in donor T cells that become Tfh cells is required for cGVHD in a nonsclerodermatous multiorgan system disease model that includes bronchiolitis obliterans (BO), dependent upon GC B cells, Tfhs, and counterbalanced by T follicular regulatory cells, each requiring PI3Kδ signaling for function and survival. Although B cells rely on PI3Kδ pathway signaling and GC formation is disrupted resulting in a substantial decrease in Ig production, PI3Kδ kinase-dead mutant donor bone marrow-derived GC B cells still supported BO cGVHD generation. A PI3Kδ-specific inhibitor, compound GS-649443, that has superior potency to idelalisib while maintaining selectivity, reduced cGVHD in mice with active disease. In a Th1-dependent and Th17-associated scleroderma model, GS-649443 effectively treated mice with active cGVHD. These data provide a foundation for clinical trials of US Food and Drug Administration (FDA)-approved PI3Kδ inhibitors for cGVHD therapy in patients.

Published
2019

25. Impact of diagnostic genetics on remission MRD and transplantation outcomes in older patients with AML

Author

Murdock, H. Moses, Kim, Haesook T., Denlinger, Nathan, Vachhani, Pankit, Hambley, Bryan, Manning, Bryan S., Gier, Shannon, Cho, Christina, Tsai, Harrison K., McCurdy, Shannon, Ho, Vincent T., Koreth, John, Soiffer, Robert J., Ritz, Jerome, Carroll, Martin P., Vasu, Sumithira, Perales, Miguel-Angel, Wang, Eunice S., Gondek, Lukasz P., Devine, Steven, Alyea, Edwin P., III, Lindsley, R. Coleman, and Gibson, Christopher J.

Published
2022
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26. A phase I trial of vaccination with lethally irradiated lymphoma cells admixed with granulocyte-macrophage colony-stimulating factor secreting K562 cells for the treatment of follicular lymphoma.

Author

Jacobsen, Eric, Plant, Ashley, Redd, Robert, Armand, Philippe, McDonough, Mikaela, Ihuoma, Udochukwu, Fisher, David C., LaCasce, Ann, Ritz, Jerome, Dranoff, Glenn, and Freedman, Arnold

Subjects
GRANULOCYTE-macrophage colony-stimulating factor, KILLER cells, FOLLICULAR lymphoma, IMMUNOLOGICAL adjuvants, T cells
Abstract

Several vaccine strategies have been tested for the treatment of follicular lymphoma; however, none have proven successful. In a phase I dose-escalation protocol, we developed a vaccine consisting of lethally irradiated whole lymphoma cells admixed with K562 cells that constitutively secreted granulocyte-macrophage colony-stimulating factor (GM-K562)(ClinicalTrials.gov identifier: NCT00487305). Patients with grade 1, 2, or 3 A follicular lymphoma were divided into 2 study tiers based on prior treatment and received a maximum of 6 vaccines. Vaccines contained dose levels of 5 × 106 or 1 × 107 GM-K562 cells admixed with autologous tumor cells at doses ranging from 1 × 105 to 5 × 107.Correlative studies did not demonstrate a significant immune response as assessed by delayed-type hypersensitivity reactions, B and T cell subsets, and natural killer cell subsets. Future vaccine studies should focus on identifying lymphoma-specific immunogenic proteins and modifying the vaccine immune adjuvant. [ABSTRACT FROM AUTHOR]

Published
2024
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27. BET-bromodomain and EZH2 inhibitor–treated chronic GVHD mice have blunted germinal centers with distinct transcriptomes

Author

Zaiken, Michael C., Flynn, Ryan, Paz, Katelyn G., Rhee, Stephanie Y., Jin, Sujeong, Mohamed, Fathima A., Saha, Asim, Thangavelu, Govindarajan, Park, Paul M.C., Hemming, Matthew L., Sage, Peter T., Sharpe, Arlene H., DuPage, Michel, Bluestone, Jeffrey A., Panoskaltsis-Mortari, Angela, Cutler, Corey S., Koreth, John, Antin, Joseph H., Soiffer, Robert J., Ritz, Jerome, Luznik, Leo, Maillard, Ivan, Hill, Geoffrey R., MacDonald, Kelli P.A., Munn, David H., Serody, Jonathan S., Murphy, William J., Kean, Leslie S., Zhang, Yi, Bradner, James E., Qi, Jun, and Blazar, Bruce R.

Published
2022
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28. GM-CSF secreting leukemia cell vaccination for MDS/AML after allogeneic HSCT: a randomized, double-blinded, phase 2 trial

Author

Ho, Vincent T., Kim, Haesook T., Brock, Jennifer, Galinsky, Ilene, Daley, Heather, Reynolds, Carol, Weber, Augustine, Pozdnyakova, Olga, Severgnini, Mariano, Nikiforow, Sarah, Cutler, Corey, Koreth, John, Alyea, Edwin P., III, Antin, Joseph H., Gooptu, Mahasweta, Romee, Rizwan, Shapiro, Roman, Chen, Yi-Bin, Rosenblatt, Jacalyn, Avigan, David, Hodi, F. Stephen, Dranoff, Glenn, Wu, Catherine J., Ritz, Jerome, and Soiffer, Robert J.

Published
2022
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31. Mapping the evolution of T cell states during response and resistance to adoptive cellular therapy

Author

Bachireddy, Pavan, Azizi, Elham, Burdziak, Cassandra, Nguyen, Vinhkhang N., Ennis, Christina S., Maurer, Katie, Park, Cameron Y., Choo, Zi-Ning, Li, Shuqiang, Gohil, Satyen H., Ruthen, Neil G., Ge, Zhongqi, Keskin, Derin B., Cieri, Nicoletta, Livak, Kenneth J., Kim, Haesook T., Neuberg, Donna S., Soiffer, Robert J., Ritz, Jerome, Alyea, Edwin P., Pe’er, Dana, and Wu, Catherine J.

Published
2021
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32. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2020 Etiology and Prevention Working Group Report

Author

Williams, Kirsten M., Inamoto, Yoshihiro, Im, Annie, Hamilton, Betty, Koreth, John, Arora, Mukta, Pusic, Iskra, Mays, Jacqueline W., Carpenter, Paul A., Luznik, Leo, Reddy, Pavan, Ritz, Jerome, Greinix, Hildegard, Paczesny, Sophie, Blazar, Bruce R., Pidala, Joseph, Cutler, Corey, Wolff, Daniel, Schultz, Kirk R., Pavletic, Steven Z., Lee, Stephanie J., Martin, Paul J., Socie, Gerard, and Sarantopoulos, Stefanie

Published
2021
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36. NKTR-358: A novel regulatory T-cell stimulator that selectively stimulates expansion and suppressive function of regulatory T cells for the treatment of autoimmune and inflammatory diseases

Author

Dixit, Neha, Fanton, Christie, Langowski, John L., Kirksey, Yolanda, Kirk, Peter, Chang, Thomas, Cetz, Janet, Dixit, Vidula, Kim, Grace, Kuo, Peiwen, Maiti, Mekhala, Tang, Yinyan, VanderVeen, Laurie A., Zhang, Ping, Lee, Myong, Ritz, Jerome, Kamihara, Yusuke, Ji, Chunmei, Rubas, Werner, Sweeney, Theresa D., Doberstein, Stephen K., and Zalevsky, Jonathan

Published
2021
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39. A multicenter phase 1 study of nivolumab for relapsed hematologic malignancies after allogeneic transplantation

Author

Davids, Matthew S., Kim, Haesook T., Costello, Caitlin, Herrera, Alex F., Locke, Frederick L., Maegawa, Rodrigo O., Savell, Alexandra, Mazzeo, Michael, Anderson, Adrienne, Boardman, Alexander P., Weber, Augustine, Avigan, David, Chen, Yi-Bin, Nikiforow, Sarah, Ho, Vincent T., Cutler, Corey, Alyea, Edwin P., Bachireddy, Pavan, Wu, Catherine J., Ritz, Jerome, Streicher, Howard, Ball, Edward D., Bashey, Asad, Soiffer, Robert J., and Armand, Philippe

Published
2020
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40. BK virus–specific T-cell immune reconstitution after allogeneic hematopoietic cell transplantation

Author

Espada, Eduardo, Cheng, Matthew P., Kim, Haesook T., Woolley, Ann E., Avigan, Jason I., Forcade, Edouard, Soares, Maria V.D., Lacerda, João F., Nikiforow, Sarah, Gooptu, Mahasweta, Romee, Rizwan, Alyea, Edwin P., Armand, Philippe, Cutler, Corey S., Ho, Vincent T., Koreth, John, Antin, Joseph H., Soiffer, Robert J., Marty, Francisco M., and Ritz, Jerome

Published
2020
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41. Phase II trial of vaccination with autologous, irradiated melanoma cells engineered by adenoviral mediated gene transfer to secrete granulocyte-macrophage colony stimulating factor in patients with stage III and IV melanoma

Author

Sussman, Tamara A., primary, Severgnini, Mariano, additional, Giobbie-Hurder, Anita, additional, Friedlander, Philip, additional, Swanson, Scott J., additional, Jaklitsch, Michael, additional, Clancy, Thomas, additional, Goguen, Laura A., additional, Lautz, David, additional, Swanson, Richard, additional, Daley, Heather, additional, Ritz, Jerome, additional, Dranoff, Glenn, additional, and Hodi, F. Stephen, additional

Published
2024
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42. Active infection at the time of CD34+ selected stem cell boost is associated with treatment failure and poor survival

Author

Shapiro, Roman M, primary, Kim, Haesook T, additional, Dulery, Remy, additional, Liney, Deborah, additional, Garrity, Heather M, additional, Panaro, Kevin M., additional, Au, Chloe, additional, Gervais, Casey, additional, Little, Jessica S., additional, Ho, Vincent T., additional, Cutler, Corey S., additional, Koreth, John, additional, Gooptu, Mahasweta, additional, Antin, Joseph H., additional, Kelkar, Amar H., additional, Romee, Rizwan, additional, Wu, Catherine J., additional, Ritz, Jerome, additional, Soiffer, Robert J., additional, and Nikiforow, Sarah, additional

Published
2024
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44. Ipilimumab for Patients with Relapse after Allogeneic Transplantation

Author

Davids, Matthew S, Kim, Haesook T, Bachireddy, Pavan, Costello, Caitlin, Liguori, Rebecca, Savell, Alexandra, Lukez, Alexander P, Avigan, David, Chen, Yi-Bin, McSweeney, Peter, LeBoeuf, Nicole R, Rooney, Michael S, Bowden, Michaela, Zhou, Chensheng W, Granter, Scott R, Hornick, Jason L, Rodig, Scott J, Hirakawa, Masahiro, Severgnini, Mariano, Hodi, F Stephen, Wu, Catherine J, Ho, Vincent T, Cutler, Corey, Koreth, John, Alyea, Edwin P, Antin, Joseph H, Armand, Philippe, Streicher, Howard, Ball, Edward D, Ritz, Jerome, Bashey, Asad, and Soiffer, Robert J

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Clinical Research, Hematology, Regenerative Medicine, Pediatric, Patient Safety, Stem Cell Research - Nonembryonic - Non-Human, Cancer, Rare Diseases, Pediatric Cancer, Clinical Trials and Supportive Activities, Stem Cell Research, Transplantation, Stem Cell Research - Nonembryonic - Human, 6.2 Cellular and gene therapies, 5.2 Cellular and gene therapies, 6.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Evaluation of treatments and therapeutic interventions, Adult, Aged, Antibodies, Monoclonal, CD4 Lymphocyte Count, Female, Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, Humans, Induction Chemotherapy, Ipilimumab, Leukemia, Lymphoma, Male, Middle Aged, Myeloproliferative Disorders, Recurrence, T-Lymphocytes, Regulatory, Transplantation Immunology, Transplantation, Homologous, Leukemia and Lymphoma Society Blood Cancer Research Partnership, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundLoss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse of hematologic cancers. We hypothesized that immune checkpoint blockade established by targeting cytotoxic T-lymphocyte-associated protein 4 with ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect.MethodsWe conducted a phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT. Patients received induction therapy with ipilimumab at a dose of 3 or 10 mg per kilogram of body weight every 3 weeks for a total of 4 doses, with additional doses every 12 weeks for up to 60 weeks in patients who had a clinical benefit.ResultsA total of 28 patients were enrolled. Immune-related adverse events, including one death, were observed in 6 patients (21%), and graft-versus-host disease (GVHD) that precluded further administration of ipilimumab was observed in 4 patients (14%). No responses that met formal response criteria occurred in patients who received a dose of 3 mg per kilogram. Among 22 patients who received a dose of 10 mg per kilogram, 5 (23%) had a complete response, 2 (9%) had a partial response, and 6 (27%) had decreased tumor burden. Complete responses occurred in 4 patients with extramedullary acute myeloid leukemia and 1 patient with the myelodysplastic syndrome developing into acute myeloid leukemia. Four patients had a durable response for more than 1 year. Responses were associated with in situ infiltration of cytotoxic CD8+ T cells, decreased activation of regulatory T cells, and expansion of subpopulations of effector T cells in the blood.ConclusionsOur early-phase data showed that administration of ipilimumab was feasible in patients with recurrent hematologic cancers after allogeneic HSCT, although immune-mediated toxic effects and GVHD occurred. Durable responses were observed in association with several histologic subtypes of these cancers, including extramedullary acute myeloid leukemia. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01822509.).

Published
2016

45. The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice

Author

Townsend, Elizabeth C, Murakami, Mark A, Christodoulou, Alexandra, Christie, Amanda L, Köster, Johannes, DeSouza, Tiffany A, Morgan, Elizabeth A, Kallgren, Scott P, Liu, Huiyun, Wu, Shuo-Chieh, Plana, Olivia, Montero, Joan, Stevenson, Kristen E, Rao, Prakash, Vadhi, Raga, Andreeff, Michael, Armand, Philippe, Ballen, Karen K, Barzaghi-Rinaudo, Patrizia, Cahill, Sarah, Clark, Rachael A, Cooke, Vesselina G, Davids, Matthew S, DeAngelo, Daniel J, Dorfman, David M, Eaton, Hilary, Ebert, Benjamin L, Etchin, Julia, Firestone, Brant, Fisher, David C, Freedman, Arnold S, Galinsky, Ilene A, Gao, Hui, Garcia, Jacqueline S, Garnache-Ottou, Francine, Graubert, Timothy A, Gutierrez, Alejandro, Halilovic, Ensar, Harris, Marian H, Herbert, Zachary T, Horwitz, Steven M, Inghirami, Giorgio, Intlekofer, Andrew M, Ito, Moriko, Izraeli, Shai, Jacobsen, Eric D, Jacobson, Caron A, Jeay, Sébastien, Jeremias, Irmela, Kelliher, Michelle A, Koch, Raphael, Konopleva, Marina, Kopp, Nadja, Kornblau, Steven M, Kung, Andrew L, Kupper, Thomas S, LeBoeuf, Nicole R, LaCasce, Ann S, Lees, Emma, Li, Loretta S, Look, A Thomas, Murakami, Masato, Muschen, Markus, Neuberg, Donna, Ng, Samuel Y, Odejide, Oreofe O, Orkin, Stuart H, Paquette, Rachel R, Place, Andrew E, Roderick, Justine E, Ryan, Jeremy A, Sallan, Stephen E, Shoji, Brent, Silverman, Lewis B, Soiffer, Robert J, Steensma, David P, Stegmaier, Kimberly, Stone, Richard M, Tamburini, Jerome, Thorner, Aaron R, van Hummelen, Paul, Wadleigh, Martha, Wiesmann, Marion, Weng, Andrew P, Wuerthner, Jens U, Williams, David A, Wollison, Bruce M, Lane, Andrew A, Letai, Anthony, Bertagnolli, Monica M, Ritz, Jerome, Brown, Myles, Long, Henry, Aster, Jon C, Shipp, Margaret A, Griffin, James D, and Weinstock, David M

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biotechnology, Clinical Trials and Supportive Activities, Orphan Drug, Clinical Research, Hematology, Cancer, Rare Diseases, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Good Health and Well Being, Animals, Antineoplastic Agents, Biomarkers, Tumor, Cell Lineage, Female, Gene Expression Profiling, Genes, p53, Heterografts, Humans, Internet, Isoquinolines, Leukemia, Leukemia, Experimental, Lymphoma, Male, Mice, Mice, Inbred NOD, Molecular Targeted Therapy, Neoplasm Proteins, Neoplasm Transplantation, Phenotype, Piperazines, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Proteome, Proto-Oncogene Proteins c-mdm2, Random Allocation, Randomized Controlled Trials as Topic, Research Design, Tissue Banks, Transcriptome, Xenograft Model Antitumor Assays, Neurosciences, Oncology & Carcinogenesis, Biochemistry and cell biology, Oncology and carcinogenesis
Abstract

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease.

Published
2016

46. PD-1 blockade for diffuse large B-cell lymphoma after autologous stem cell transplantation

Author

Frigault, Matthew J., Armand, Philippe, Redd, Robert A., Jeter, Erin, Merryman, Reid W., Coleman, Kimberly C., Herrera, Alex F., Dahi, Parastoo, Nieto, Yago, LaCasce, Ann S., Fisher, David C., Ng, Samuel Y., Odejide, Oreife O., Freedman, Arnold S., Kim, Austin I., Crombie, Jennifer L., Jacobson, Caron A., Jacobsen, Eric D., Wong, Jeffrey L., Bsat, Jad, Patel, Sanjay S., Ritz, Jerome, Rodig, Scott J., Shipp, Margaret A., Chen, Yi-Bin, and Joyce, Robin M.

Published
2020
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47. Inhibition of inositol kinase B controls acute and chronic graft-versus-host disease

Author

Thangavelu, Govindarajan, Du, Jing, Paz, Katelyn G., Loschi, Michael, Zaiken, Michael C., Flynn, Ryan, Taylor, Patricia A., Kirchmeier, Andrew Kemal, Panoskaltsis-Mortari, Angela, Luznik, Leo, MacDonald, Kelli P., Hill, Geoffrey R., Maillard, Ivan, Munn, David H., Serody, Jonathan S., Murphy, William J., Miklos, David, Cutler, Corey S., Koreth, John, Antin, Joseph H., Soiffer, Robert J., Ritz, Jerome, Dahlberg, Carol, Miller, Andrew T., and Blazar, Bruce R.

Published
2020
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48. Peripheral host T cells survive hematopoietic stem cell transplantation and promote graft-versus-host disease

Author

Divito, Sherrie J., Aasebo, Anders T., Matos, Tiago R., Hsieh, Pei-Chen, Collin, Matthew, Elco, Christopher P., O'Malley, John T., Baekkevold, Espen S., Reims, Henrik, Gedde-Dahl, Tobias, Hagerstrom, Michael, Hilaire, Jude, Lian, John W., Milford, Edgar L., Pinkus, Geraldine S., Ho, Vincent T., Soiffer, Robert J., Kim, Haesook T., Mihm, Martin C., Ritz, Jerome, Guleria, Indira, Cutler, Corey S., Clark, Rachael A., Jahnsen, Frode L., and Kupper, Thomas S.

Subjects
Thermo Fisher Scientific Inc., Health aspects, Medical research -- Health aspects, Skin -- Health aspects, Hematopoietic stem cell transplantation -- Health aspects, Stem cells -- Health aspects, Scientific equipment industry -- Health aspects, T cells -- Health aspects
Abstract

Introduction Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) (1-6). Current dogma holds that donor T cells, either transferred with or [...], Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT). Donor T cells are key mediators in pathogenesis, but a contribution from host T cells has not been explored, as conditioning regimens are believed to deplete host T cells. To evaluate a potential role for host T cells in GVHD, the origin of skin and blood T cells was assessed prospectively in patients after HSCT in the absence of GVHD. While blood contained primarily donor-derived T cells, most T cells in the skin were host derived. We next examined patient skin, colon, and blood during acute GVHD. Host T cells were present in all skin and colon acute GVHD specimens studied, yet were largely absent in blood. We observed acute skin GVHD in the presence of 100% host T cells. Analysis demonstrated that a subset of host T cells in peripheral tissues were proliferating ([Ki67.sup.+]) and producing the proinflammatory cytokines IFN-[gamma] and IL-17 in situ. Comparatively, the majority of antigen-presenting cells (APCs) in tissue in acute GVHD were donor derived, and donor-derived APCs were observed directly adjacent to host T cells. A humanized mouse model demonstrated that host skin-resident T cells could be activated by donor monocytes to generate a GVHD-like dermatitis. Thus, host tissue-resident T cells may play a previously unappreciated pathogenic role in acute GVHD.

Published
2020
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50. Oncogene-induced TIM-3 ligand expression dictates susceptibility to anti-TIM-3 therapy in mice

Author

Talvard-Balland, Nana, Braun, Lukas M; https://orcid.org/0000-0003-0770-4994, Dixon, Karen O; https://orcid.org/0000-0001-7811-5439, Zwick, Melissa, Engel, Helena; https://orcid.org/0000-0001-9792-7694, Hartmann, Alina, Duquesne, Sandra; https://orcid.org/0000-0002-9133-6065, Penter, Livius, Andrieux, Geoffroy; https://orcid.org/0000-0002-5389-9481, Rindlisbacher, Lukas; https://orcid.org/0000-0002-9408-1336, Acerbis, Andrea, Ehmann, Jule, Köllerer, Christoph, Ansuinelli, Michela, Rettig, Andres, Moschallski, Kevin, Apostolova, Petya; https://orcid.org/0000-0002-3856-5109, Brummer, Tilman; https://orcid.org/0000-0003-4387-7905, Illert, Anna L, Schramm, Markus A, Cheng, Yurong, Köttgen, Anna, Duyster, Justus; https://orcid.org/0009-0003-1497-3954, Menssen, Hans D; https://orcid.org/0000-0002-1895-4713, Ritz, Jerome, Blazar, Bruce R; https://orcid.org/0000-0002-9608-9841, Boerries, Melanie; https://orcid.org/0000-0002-3670-0602, Schmitt-Gräff, Annette, Sariipek, Nurefsan, Wertheimer, Tobias; https://orcid.org/0000-0002-8480-7391, et al, Talvard-Balland, Nana, Braun, Lukas M; https://orcid.org/0000-0003-0770-4994, Dixon, Karen O; https://orcid.org/0000-0001-7811-5439, Zwick, Melissa, Engel, Helena; https://orcid.org/0000-0001-9792-7694, Hartmann, Alina, Duquesne, Sandra; https://orcid.org/0000-0002-9133-6065, Penter, Livius, Andrieux, Geoffroy; https://orcid.org/0000-0002-5389-9481, Rindlisbacher, Lukas; https://orcid.org/0000-0002-9408-1336, Acerbis, Andrea, Ehmann, Jule, Köllerer, Christoph, Ansuinelli, Michela, Rettig, Andres, Moschallski, Kevin, Apostolova, Petya; https://orcid.org/0000-0002-3856-5109, Brummer, Tilman; https://orcid.org/0000-0003-4387-7905, Illert, Anna L, Schramm, Markus A, Cheng, Yurong, Köttgen, Anna, Duyster, Justus; https://orcid.org/0009-0003-1497-3954, Menssen, Hans D; https://orcid.org/0000-0002-1895-4713, Ritz, Jerome, Blazar, Bruce R; https://orcid.org/0000-0002-9608-9841, Boerries, Melanie; https://orcid.org/0000-0002-3670-0602, Schmitt-Gräff, Annette, Sariipek, Nurefsan, Wertheimer, Tobias; https://orcid.org/0000-0002-8480-7391, and et al

Published
2024

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