Search

Your search keyword '"DiPersio, John F."' showing total 2,912 results
Start Over Author "DiPersio, John F."
2,912 results on '"DiPersio, John F."'

1. Monitoring clonal burden as an alternative to blast count for myelodysplastic neoplasm treatment response: EARLY PHASE STUDIES

Author

Jacoby, Meagan A., Duncavage, Eric D., Khanna, Ajay, Chang, Gue Su, Nonavinkere Srivatsan, Sridhar, Miller, Christopher A., Gao, Feng, Robinson, Josh, Shao, Jin, Fulton, Robert S., Fronick, Catrina C., O’Laughlin, Michelle, Heath, Sharon E., Brendel, Kimberly, Chavez, Monique, DiPersio, John F., Abboud, Camille N., Stockerl-Goldstein, Keith, Westervelt, Peter, Cashen, Amanda, Pusic, Iskra, Oh, Stephen T., Welch, John S., Wells, Denise A., Loken, Michael R., Uy, Geoffrey L., and Walter, Matthew J.

Published
2025
Full Text
View/download PDF

2. Germline predisposition in multiple myeloma

Author

Martins Rodrigues, Fernanda, Jasielec, Jagoda, Perpich, Melody, Kim, Aelin, Moma, Luke, Li, Yize, Storrs, Erik, Wendl, Michael C., Jayasinghe, Reyka G., Fiala, Mark, Stefka, Andrew, Derman, Benjamin, Jakubowiak, Andrzej J., DiPersio, John F., Vij, Ravi, Godley, Lucy A., and Ding, Li

Published
2025
Full Text
View/download PDF

5. Epigenetic regulation during cancer transitions across 11 tumour types

Author

Terekhanova, Nadezhda V., Karpova, Alla, Liang, Wen-Wei, Strzalkowski, Alexander, Chen, Siqi, Li, Yize, Southard-Smith, Austin N., Iglesia, Michael D., Wendl, Michael C., Jayasinghe, Reyka G., Liu, Jingxian, Song, Yizhe, Cao, Song, Houston, Andrew, Liu, Xiuting, Wyczalkowski, Matthew A., Lu, Rita Jui-Hsien, Caravan, Wagma, Shinkle, Andrew, Naser Al Deen, Nataly, Herndon, John M., Mudd, Jacqueline, Ma, Cong, Sarkar, Hirak, Sato, Kazuhito, Ibrahim, Omar M., Mo, Chia-Kuei, Chasnoff, Sara E., Porta-Pardo, Eduard, Held, Jason M., Pachynski, Russell, Schwarz, Julie K., Gillanders, William E., Kim, Albert H., Vij, Ravi, DiPersio, John F., Puram, Sidharth V., Chheda, Milan G., Fuh, Katherine C., DeNardo, David G., Fields, Ryan C., Chen, Feng, Raphael, Benjamin J., and Ding, Li

Published
2023
Full Text
View/download PDF

7. 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
Full Text
View/download PDF

11. Itacitinib for prevention of graft-versus-host disease and cytokine release syndrome in haploidentical transplantation

Author

Abboud, Ramzi, Schroeder, Mark A., Rettig, Michael P., Jayasinghe, Reyka G., Gao, Feng, Eisele, Jeremy, Gehrs, Leah, Ritchey, Julie, Choi, Jaebok, Abboud, Camille N., Pusic, Iskra, Jacoby, Meagan, Westervelt, Peter, Christopher, Matthew, Cashen, Amanda, Ghobadi, Armin, Stockerl-Goldstein, Keith, Uy, Geoffrey L., and DiPersio, John F.

Published
2024
Full Text
View/download PDF

12. Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial

Author

Crees, Zachary D., Rettig, Michael P., Jayasinghe, Reyka G., Stockerl-Goldstein, Keith, Larson, Sarah M., Arpad, Illes, Milone, Giulio A., Martino, Massimo, Stiff, Patrick, Sborov, Douglas, Pereira, Denise, Micallef, Ivana, Moreno-Jiménez, Gemma, Mikala, Gabor, Coronel, Maria Liz Paciello, Holtick, Udo, Hiemenz, John, Qazilbash, Muzaffar H., Hardy, Nancy, Latif, Tahir, García-Cadenas, Irene, Vainstein-Haras, Abi, Sorani, Ella, Gliko-Kabir, Irit, Goldstein, Inbal, Ickowicz, Debby, Shemesh-Darvish, Liron, Kadosh, Shaul, Gao, Feng, Schroeder, Mark A., Vij, Ravi, and DiPersio, John F.

Published
2023
Full Text
View/download PDF

13. Off-the-Shelf CAR-T

Author

Cooper, Matthew L., Ottaviano, Giorgio, DiPersio, John F., Qasim, Waseem, Teicher, Beverly A., Series Editor, Ghobadi, Armin, editor, and DiPersio, John F., editor

Published
2022
Full Text
View/download PDF

14. Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment

Author

Sun, Hua, Cao, Song, Mashl, R Jay, Mo, Chia-Kuei, Zaccaria, Simone, Wendl, Michael C, Davies, Sherri R, Bailey, Matthew H, Primeau, Tina M, Hoog, Jeremy, Mudd, Jacqueline L, Dean, Dennis A, Patidar, Rajesh, Chen, Li, Wyczalkowski, Matthew A, Jayasinghe, Reyka G, Rodrigues, Fernanda Martins, Terekhanova, Nadezhda V, Li, Yize, Lim, Kian-Huat, Wang-Gillam, Andrea, Van Tine, Brian A, Ma, Cynthia X, Aft, Rebecca, Fuh, Katherine C, Schwarz, Julie K, Zevallos, Jose P, Puram, Sidharth V, Dipersio, John F, Davis-Dusenbery, Brandi, Ellis, Matthew J, Lewis, Michael T, Davies, Michael A, Herlyn, Meenhard, Fang, Bingliang, Roth, Jack A, Welm, Alana L, Welm, Bryan E, Meric-Bernstam, Funda, Chen, Feng, Fields, Ryan C, Li, Shunqiang, Govindan, Ramaswamy, Doroshow, James H, Moscow, Jeffrey A, Evrard, Yvonne A, Chuang, Jeffrey H, Raphael, Benjamin J, and Ding, Li

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Oncology and Carcinogenesis, Cancer, Human Genome, Biotechnology, Cancer Genomics, Good Health and Well Being, Animals, Disease Models, Animal, Female, Gene Expression Regulation, Neoplastic, Genome, Genomics, Heterografts, Humans, Male, Mice, Models, Biological, Mutation, Neoplasms, Transcriptome, Xenograft Model Antitumor Assays, NCI PDXNet Consortium
Abstract

Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs' recapitulation of human tumors.

Published
2021

16. Genomic landscape of TP53-mutated myeloid malignancies

Author

Abel, Haley J., Oetjen, Karolyn A., Miller, Christopher A., Ramakrishnan, Sai M., Day, Ryan B., Helton, Nichole M., Fronick, Catrina C., Fulton, Robert S., Heath, Sharon E., Tarnawsky, Stefan P., Nonavinkere Srivatsan, Sridhar, Duncavage, Eric J., Schroeder, Molly C., Payton, Jacqueline E., Spencer, David H., Walter, Matthew J., Westervelt, Peter, DiPersio, John F., Ley, Timothy J., and Link, Daniel C.

Published
2023
Full Text
View/download PDF

17. A phase 1 trial of itacitinib, a selective JAK1 inhibitor, in patients with acute graft-versus-host disease

Author

Schroeder, Mark A, Khoury, H Jean, Jagasia, Madan, Ali, Haris, Schiller, Gary J, Staser, Karl, Choi, Jaebok, Gehrs, Leah, Arbushites, Michael C, Yan, Ying, Langmuir, Peter, Srinivas, Nithya, Pratta, Michael, Perales, Miguel-Angel, Chen, Yi-Bin, Meyers, Gabrielle, and DiPersio, John F

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Stem Cell Research - Nonembryonic - Human, Hematology, Clinical Trials and Supportive Activities, Stem Cell Research, Rare Diseases, Orphan Drug, Clinical Research, Transplantation, 6.1 Pharmaceuticals, 6.2 Cellular and gene therapies, Evaluation of treatments and therapeutic interventions, Adolescent, Adrenal Cortex Hormones, Adult, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Janus Kinase 1, Protein Kinase Inhibitors, Steroids, Cardiovascular medicine and haematology
Abstract

Acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic cell transplantation (HCT) is a primary cause of nonrelapse mortality and a major barrier to successful transplant outcomes. Itacitinib is a Janus kinase (JAK)1-selective inhibitor that has demonstrated efficacy in preclinical models of aGVHD. We report results from the first registered study of a JAK inhibitor in patients with aGVHD. This was an open-label phase 1 study enrolling patients aged ≥18 years with first HCT from any source who developed grade IIB to IVD aGVHD. Patients with steroid-naive or steroid-refractory aGVHD were randomized 1:1 to itacitinib 200 mg or 300 mg once daily plus corticosteroids. The primary endpoint was safety and tolerability; day 28 overall response rate (ORR) was the main secondary endpoint. Twenty-nine patients (200 mg, n = 14; 300 mg, n = 15) received ≥1 dose of itacitinib and were included in safety and efficacy assessments. One dose-limiting toxicity was reported (grade 3 thrombocytopenia attributed to GVHD progression in a patient receiving 300 mg itacitinib with preexisting thrombocytopenia). The most common nonhematologic treatment-emergent adverse event was diarrhea (48.3%, n = 14); anemia occurred in 11 patients (38%). ORR on day 28 for all patients in the 200-mg and 300-mg groups was 78.6% and 66.7%, respectively. Day 28 ORR was 75.0% for patients with treatment-naive aGVHD and 70.6% in those with steroid-refractory aGVHD. All patients receiving itacitinib decreased corticosteroid use over time. In summary, itacitinib was well tolerated and demonstrated encouraging efficacy in patients with steroid-naive or steroid-refractory aGVHD, warranting continued clinical investigations. This trial was registered at www.clinicaltrials.gov as #NCT02614612.

Published
2020

18. Apolipoprotein M Attenuates Anthracycline Cardiotoxicity and Lysosomal Injury

Author

Guo, Zhen, Valenzuela Ripoll, Carla, Picataggi, Antonino, Rawnsley, David R., Ozcan, Mualla, Chirinos, Julio A., Chendamarai, Ezhilarasi, Girardi, Amanda, Riehl, Terrence, Evie, Hosannah, Diab, Ahmed, Kovacs, Attila, Hyrc, Krzysztof, Ma, Xiucui, Asnani, Aarti, Shewale, Swapnil V., Scherrer-Crosbie, Marielle, Cowart, Lauren Ashley, Parks, John S., Zhao, Lei, Gordon, David, Ramirez-Valle, Francisco, Margulies, Kenneth B., Cappola, Thomas P., Desai, Ankit A., Pedersen, Lauren N., Bergom, Carmen, Stitziel, Nathan O., Rettig, Michael P., DiPersio, John F., Hajny, Stefan, Christoffersen, Christina, Diwan, Abhinav, and Javaheri, Ali

Published
2023
Full Text
View/download PDF

19. Immunosuppression and outcomes in adult patients with de novo acute myeloid leukemia with normal karyotypes

Author

Ferraro, Francesca, Miller, Christopher A., Christensen, Keegan A., Helton, Nichole M., O’Laughlin, Margaret, Fronick, Catrina C., Fulton, Robert S., Kohlschmidt, Jessica, Eisfeld, Ann-Kathrin, Bloomfield, Clara D., Ramakrishnan, Sai Mukund, Day, Ryan B., Wartman, Lukas D., Uy, Geoffrey L., Welch, John S., Christopher, Matthew J., Heath, Sharon E., Baty, Jack D., Schuelke, Matthew J., Payton, Jacqueline E., Spencer, David H., Rettig, Michael P., Link, Daniel C., Walter, Matthew J., Westervelt, Peter, DiPersio, John F., and Ley, Timothy J.

Published
2021

20. A Phase I Study of the Combination of Rituximab and Ipilimumab in Patients with Relapsed/Refractory B-Cell Lymphoma

Author

Tuscano, Joseph M, Maverakis, Emanual, Groshen, Susan, Tsao-Wei, Denice, Luxardi, Guillaume, Merleev, Alexander A, Beaven, Anne, DiPersio, John F, Popplewell, Leslie, Chen, Robert, Kirschbaum, Mark, Schroeder, Mark A, and Newman, Edward M

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Oncology and Carcinogenesis, Clinical Trials and Supportive Activities, Cancer, Lymphatic Research, Hematology, Clinical Research, Rare Diseases, Lymphoma, 6.1 Pharmaceuticals, 6.2 Cellular and gene therapies, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Drug Resistance, Neoplasm, Female, Follow-Up Studies, Humans, Ipilimumab, Lymphoma, B-Cell, Male, Middle Aged, Neoplasm Recurrence, Local, Prognosis, Rituximab, Salvage Therapy, Survival Rate, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

PurposeBased on the potential for ipilimumab (I) to augment T-cell activation, we hypothesize that ipilimumab would augment the efficacy of rituximab (R) in patients with relapsed/refractory (R/R) CD20+non-Hodgkin's lymphoma (NHL). This phase I study aimed to identify a recommended phase 2 dose, document toxicities, and preliminarily assess efficacy and potential predictive biomarkers.Patients and methodsThirty-three patients with R/R CD20+B-cell lymphoma received R at 375 mg/m2weekly for 4 weeks and I at 3 mg/kg on day 1 and every 3 weeks for four doses. Responding patients went on to maintenance with each agent given every 12 weeks. To facilitate correlative analysis, the expansion phase randomized patients to simultaneous R+I versus R with I delayed 2 weeks.ResultsToxicity was manageable; no dose-limiting toxicity was observed at the doses studied. When considering the entire cohort, efficacy was modest, with an objective response rate (ORR) of 24% and median progression-free survival (PFS) of 2.6 months. However, in follicular lymphoma patients, the ORR was 58% with a median PFS of 5.6 months. The randomized comparison of R with R+I demonstrated that R+I resulted in more effective B-cell depletion (BCD). Both B-cell depletion and the ratio of CD45RA-regulatory T cell (Treg) to Treg were associated with response at all time points.ConclusionsThe combination of R+I has manageable toxicity and encouraging efficacy in R/R follicular lymphoma. The ratio of CD45RA-Tregs to total Tregs, and peripheral BCD should be studied further as potential predictors of response.

Published
2019

21. Clinical utilization of Chimeric Antigen Receptor T-cells (CAR-T) in B-cell acute lymphoblastic leukemia (ALL)–an expert opinion from the European Society for Blood and Marrow Transplantation (EBMT) and the American Society for Blood and Marrow Transplantation (ASBMT)

Author

Kansagra, Ankit J, Frey, Noelle V, Bar, Merav, Laetsch, Theodore W, Carpenter, Paul A, Savani, Bipin N, Heslop, Helen E, Bollard, Catherine M, Komanduri, Krishna V, Gastineau, Dennis A, Chabannon, Christian, Perales, Miguel A, Hudecek, Michael, Aljurf, Mahmoud, Andritsos, Leslie, Barrett, John A, Bachanova, Veronika, Bonini, Chiara, Ghobadi, Armin, Gill, Saar I, Hill, Joshua A, Kenderian, Saad, Kebriaei, Partow, Nagler, Arnon, Maloney, David, Liu, Hien D, Shah, Nirali N, Kharfan-Dabaja, Mohamed A, Shpall, Elizabeth J, Mufti, Ghulam J, Johnston, Laura, Jacoby, Elad, Bazarbachi, Ali, DiPersio, John F, Pavletic, Steven Z, Porter, David L, Grupp, Stephan A, Sadelain, Michel, Litzow, Mark R, Mohty, Mohamad, and Hashmi, Shahrukh K

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Cancer, Pediatric, Childhood Leukemia, Immunization, Genetics, Transplantation, Biotechnology, Gene Therapy, Pediatric Cancer, Pediatric Research Initiative, Hematology, Orphan Drug, Rare Diseases, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Good Health and Well Being, Clinical Sciences, Cardiovascular medicine and haematology, Oncology and carcinogenesis
Abstract

On August 30, 2017, the U.S. Food and Drug Administration (US-FDA) approved tisagenlecleucel (KYMRIAH, Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor-T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring and disease assessments. To address these issues, experts representing the American Society for Blood and Marrow Transplant (ASBMT), the European Group for Blood and Marrow Transplantation (EBMT), the International Society of Cell and Gene Therapy (ISCT), and the Foundation for the Accreditation of Cellular Therapy (FACT), formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.

Published
2019

22. Clinical Utilization of Chimeric Antigen Receptor T Cells in B Cell Acute Lymphoblastic Leukemia: An Expert Opinion from the European Society for Blood and Marrow Transplantation and the American Society for Transplantation and Cellular Therapy

Author

Kansagra, Ankit J, Frey, Noelle V, Bar, Merav, Laetsch, Theodore W, Carpenter, Paul A, Savani, Bipin N, Heslop, Helen E, Bollard, Catherine M, Komanduri, Krishna V, Gastineau, Dennis A, Chabannon, Christian, Perales, Miguel A, Hudecek, Michael, Aljurf, Mahmoud, Andritsos, Leslie, Barrett, John A, Bachanova, Veronika, Bonini, Chiara, Ghobadi, Armin, Gill, Saar I, Hill, Joshua, Kenderian, Saad, Kebriaei, Partow, Nagler, Arnon, Maloney, David, Liu, Hien D, Shah, Nirali N, Kharfan-Dabaja, Mohamed A, Shpall, Elizabeth J, Mufti, Ghulam J, Johnston, Laura, Jacoby, Elad, Bazarbachi, Ali, DiPersio, John F, Pavletic, Steven Z, Porter, David L, Grupp, Stephan A, Sadelain, Michel, Litzow, Mark R, Mohty, Mohamad, and Hashmi, Shahrukh K

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Transplantation, Childhood Leukemia, Pediatric Cancer, Pediatric, Biotechnology, Orphan Drug, Genetics, Pediatric Research Initiative, Cancer, Rare Diseases, Gene Therapy, Immunization, Hematology, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Good Health and Well Being, Antigens, CD19, Child, Critical Pathways, Drug Approval, Expert Testimony, Humans, Immunotherapy, Adoptive, Practice Patterns, Physicians', Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Receptors, Antigen, T-Cell, Societies, Medical, United States, Young Adult, Chimeric antigen receptor, Leukemia, T cell, Clinical Sciences, Cardiovascular medicine and haematology
Abstract

On August 30, 2017 the US Food and Drug Administration approved tisagenlecleucel (Kymriah; Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present, ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring, and disease assessments. To address these issues experts representing the American Society for Blood and Marrow Transplant, the European Society for Blood and Marrow Transplantation, the International Society of Cell and Gene Therapy, and the Foundation for the Accreditation of Cellular Therapy formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved.

Published
2019

23. The role of allogeneic transplant for adult Ph+ ALL in CR1 with complete molecular remission: a retrospective analysis

Author

Ghobadi, Armin, Slade, Michael, Kantarjian, Hagop, Alvarenga, Julio, Aldoss, Ibrahim, Mohammed, Kahee A., Jabbour, Elias, Faramand, Rawan, Shah, Bijal, Locke, Frederick, Fingrut, Warren, Park, Jae H., Short, Nicholas J., Gao, Feng, Uy, Geoffrey L., Westervelt, Peter, DiPersio, John F., Champlin, Richard E., Al Malki, Monzr M., Ravandi, Farhad, and Kebriaei, Partow

Published
2022
Full Text
View/download PDF

25. Proteomic and phosphoproteomic landscapes of acute myeloid leukemia

Author

Kramer, Michael H., Zhang, Qiang, Sprung, Robert, Day, Ryan B., Erdmann-Gilmore, Petra, Li, Yang, Xu, Ziheng, Helton, Nichole M., George, Daniel R., Mi, Yiling, Westervelt, Peter, Payton, Jacqueline E., Ramakrishnan, Sai M., Miller, Christopher A., Link, Daniel C., DiPersio, John F., Walter, Matthew J., Townsend, R. Reid, and Ley, Timothy J.

Published
2022
Full Text
View/download PDF

27. CS1 CAR-T targeting the distal domain of CS1 (SLAMF7) shows efficacy in high tumor burden myeloma model despite fratricide of CD8+CS1 expressing CAR-T cells

Author

O’Neal, Julie, Ritchey, Julie K., Cooper, Matthew L., Niswonger, Jessica, Sofía González, L., Street, Emily, Rettig, Michael P., Gladney, Susan W., Gehrs, Leah, Abboud, Ramzi, Prior, Julie L., Haas, Gabriel J., Jayasinghe, Reyka G., Ding, Li, Ghobadi, Armin, Vij, Ravi, and DiPersio, John F.

Published
2022
Full Text
View/download PDF

31. Transfer of Cell-Surface Antigens by Scavenger Receptor CD36 Promotes Thymic Regulatory T Cell Receptor Repertoire Development and Allo-tolerance

Author

Perry, Justin SA, Russler-Germain, Emilie V, Zhou, You W, Purtha, Whitney, Cooper, Matthew L, Choi, Jaebok, Schroeder, Mark A, Salazar, Vanessa, Egawa, Takeshi, Lee, Byeong-Chel, Abumrad, Nada A, Kim, Brian S, Anderson, Mark S, DiPersio, John F, and Hsieh, Chyi-Song

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Immunology, Biotechnology, Transplantation, 2.1 Biological and endogenous factors, Aetiology, Underpinning research, 1.1 Normal biological development and functioning, Inflammatory and immune system, Animals, Antigens, Surface, Bone Marrow Transplantation, CD36 Antigens, CD8 Antigens, Dendritic Cells, Epithelial Cells, Immune Tolerance, Mice, Inbred BALB C, Mice, Knockout, Mice, Transgenic, Receptors, Antigen, T-Cell, T-Lymphocytes, Regulatory, Thymus Gland, Transplantation, Homologous, CD36, antigen transfer, apoptotic cell clearance, efferocytosis, medullary thymic epithelial cells, regulatory T cells, scavenger receptor, thymic dendritic cells, tolerance
Abstract

The development of T cell tolerance in the thymus requires the presentation of host proteins by multiple antigen-presenting cell (APC) types. However, the importance of transferring host antigens from transcription factor AIRE-dependent medullary thymic epithelial cells (mTECs) to bone marrow (BM) APCs is unknown. We report that antigen was primarily transferred from mTECs to CD8α+ dendritic cells (DCs) and showed that CD36, a scavenger receptor selectively expressed on CD8α+ DCs, mediated the transfer of cell-surface, but not cytoplasmic, antigens. The absence of CD8α+ DCs or CD36 altered thymic T cell selection, as evidenced by TCR repertoire analysis and the loss of allo-tolerance in murine allogeneic BM transplantation (allo-BMT) studies. Decreases in these DCs and CD36 expression in peripheral blood of human allo-BMT patients correlated with graft-versus-host disease. Our findings suggest that CD36 facilitates transfer of mTEC-derived cell-surface antigen on CD8α+ DCs to promote tolerance to host antigens during homeostasis and allo-BMT.

Published
2018

32. Pathogenic Germline Variants in 10,389 Adult Cancers.

Author

Huang, Kuan-Lin, Mashl, R Jay, Wu, Yige, Ritter, Deborah I, Wang, Jiayin, Oh, Clara, Paczkowska, Marta, Reynolds, Sheila, Wyczalkowski, Matthew A, Oak, Ninad, Scott, Adam D, Krassowski, Michal, Cherniack, Andrew D, Houlahan, Kathleen E, Jayasinghe, Reyka, Wang, Liang-Bo, Zhou, Daniel Cui, Liu, Di, Cao, Song, Kim, Young Won, Koire, Amanda, McMichael, Joshua F, Hucthagowder, Vishwanathan, Kim, Tae-Beom, Hahn, Abigail, Wang, Chen, McLellan, Michael D, Al-Mulla, Fahd, Johnson, Kimberly J, Cancer Genome Atlas Research Network, Lichtarge, Olivier, Boutros, Paul C, Raphael, Benjamin, Lazar, Alexander J, Zhang, Wei, Wendl, Michael C, Govindan, Ramaswamy, Jain, Sanjay, Wheeler, David, Kulkarni, Shashikant, Dipersio, John F, Reimand, Jüri, Meric-Bernstam, Funda, Chen, Ken, Shmulevich, Ilya, Plon, Sharon E, Chen, Feng, and Ding, Li

Subjects
Cancer Genome Atlas Research Network, Germ Cells, Humans, Neoplasms, Genetic Predisposition to Disease, Tumor Suppressor Proteins, Gene Deletion, Gene Frequency, Genotype, Loss of Heterozygosity, Germ-Line Mutation, Mutation, Missense, Polymorphism, Single Nucleotide, Databases, Genetic, Proto-Oncogene Proteins c-met, Proto-Oncogene Proteins c-ret, DNA Copy Number Variations, LOH, cancer predisposition, germline and somatic genomes, variant pathogenicity, Cancer, Rare Diseases, Genetics, 2.1 Biological and endogenous factors, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events. We also discovered 33 such variants in oncogenes, including missenses in MET, RET, and PTPN11 associated with high gene expression. We nominated 47 additional predisposition variants from prioritized VUSs supported by multiple evidences involving case-control frequency, loss of heterozygosity, expression effect, and co-localization with mutations and modified residues. Our integrative approach links rare predisposition variants to functional consequences, informing future guidelines of variant classification and germline genetic testing in cancer.

Published
2018

34. Author Correction: Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment

Author

Sun, Hua, Cao, Song, Mashl, R. Jay, Mo, Chia-Kuei, Zaccaria, Simone, Wendl, Michael C., Davies, Sherri R., Bailey, Matthew H., Primeau, Tina M., Hoog, Jeremy, Mudd, Jacqueline L., Dean, II, Dennis A., Patidar, Rajesh, Chen, Li, Wyczalkowski, Matthew A., Jayasinghe, Reyka G., Rodrigues, Fernanda Martins, Terekhanova, Nadezhda V., Li, Yize, Lim, Kian-Huat, Wang-Gillam, Andrea, Van Tine, Brian A., Ma, Cynthia X., Aft, Rebecca, Fuh, Katherine C., Schwarz, Julie K., Zevallos, Jose P., Puram, Sidharth V., Dipersio, John F., Davis-Dusenbery, Brandi, Ellis, Matthew J., Lewis, Michael T., Davies, Michael A., Herlyn, Meenhard, Fang, Bingliang, Roth, Jack A., Welm, Alana L., Welm, Bryan E., Meric-Bernstam, Funda, Chen, Feng, Fields, Ryan C., Li, Shunqiang, Govindan, Ramaswamy, Doroshow, James H., Moscow, Jeffrey A., Evrard, Yvonne A., Chuang, Jeffrey H., Raphael, Benjamin J., and Ding, Li

Published
2022
Full Text
View/download PDF

39. Flotetuzumab as salvage immunotherapy for refractory acute myeloid leukemia

Author

Uy, Geoffrey L., Aldoss, Ibrahim, Foster, Matthew C., Sayre, Peter H., Wieduwilt, Matthew J., Advani, Anjali S., Godwin, John E., Arellano, Martha L., Sweet, Kendra L., Emadi, Ashkan, Ravandi, Farhad, Erba, Harry P., Byrne, Michael, Michaelis, Laura, Topp, Max S., Vey, Norbert, Ciceri, Fabio, Carrabba, Matteo Giovanni, Paolini, Stefania, Huls, Gerwin A., Jongen-Lavrencic, Mojca, Wermke, Martin, Chevallier, Patrice, Gyan, Emmanuel, Récher, Christian, Stiff, Patrick J., Pettit, Kristen M., Löwenberg, Bob, Church, Sarah E., Anderson, Erica, Vadakekolathu, Jayakumar, Santaguida, Marianne, Rettig, Michael P., Muth, John, Curtis, Teia, Fehr, Erin, Guo, Kuo, Zhao, Jian, Bakkacha, Ouiam, Jacobs, Kenneth, Tran, Kathy, Kaminker, Patrick, Kostova, Maya, Bonvini, Ezio, Walter, Roland B., Davidson-Moncada, Jan K., Rutella, Sergio, and DiPersio, John F.

Published
2021
Full Text
View/download PDF

43. ReCARving the future: bridging CAR T-cell therapy gaps with synthetic biology, engineering, and economic insights.

Author

Ali, Alaa and DiPersio, John F.

Subjects
CHIMERIC antigen receptors, SYNTHETIC biology, GENOME editing, T cells, CANCER treatment
Abstract

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of hematologic malignancies, offering remarkable remission rates in otherwise refractory conditions. However, its expansion into broader oncological applications faces significant hurdles, including limited efficacy in solid tumors, safety concerns related to toxicity, and logistical challenges in manufacturing and scalability. This review critically examines the latest advancements aimed at overcoming these obstacles, highlighting innovations in CAR T-cell engineering, novel antigen targeting strategies, and improvements in delivery and persistence within the tumor microenvironment. We also discuss the development of allogeneic CAR T cells as off-the-shelf therapies, strategies to mitigate adverse effects, and the integration of CAR T cells with other therapeutic modalities. This comprehensive analysis underscores the synergistic potential of these strategies to enhance the safety, efficacy, and accessibility of CAR T-cell therapies, providing a forward-looking perspective on their evolutionary trajectory in cancer treatment. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

44. Traversing the bench to bedside journey for iNKT cell therapies.

Author

O'Neal, Julie, Mavers, Melissa, Jayasinghe, Reyka G., and DiPersio, John F.

Subjects
GRAFT versus host disease, KILLER cells, CYTOTOXIC T cells, CHIMERIC antigen receptors, HEMATOPOIETIC stem cells
Abstract

Invariant natural killer T (iNKT) cells are immune cells that harness properties of both the innate and adaptive immune system and exert multiple functions critical for the control of various diseases. Prevention of graft-versus-host disease (GVHD) by iNKT cells has been demonstrated in mouse models and in correlative human studies in which high iNKT cell content in the donor graft is associated with reduced GVHD in the setting of allogeneic hematopoietic stem cell transplants. This suggests that approaches to increase the number of iNKT cells in the setting of an allogeneic transplant may reduce GVHD. iNKT cells can also induce cytolysis of tumor cells, and murine experiments demonstrate that activating iNKT cells in vivo or treating mice with ex vivo expanded iNKT cells can reduce tumor burden. More recently, research has focused on testing anti-tumor efficacy of iNKT cells genetically modified to express a chimeric antigen receptor (CAR) protein (CAR-iNKT) cells to enhance iNKT cell tumor killing. Further, several of these approaches are now being tested in clinical trials, with strong safety signals demonstrated, though efficacy remains to be established following these early phase clinical trials. Here we review the progress in the field relating to role of iNKT cells in GVHD prevention and anti- cancer efficacy. Although the iNKT field is progressing at an exciting rate, there is much to learn regarding iNKT cell subset immunophenotype and functional relationships, optimal ex vivo expansion approaches, ideal treatment protocols, need for cytokine support, and rejection risk of iNKT cells in the allogeneic setting. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

45. Development of VLA4 and CXCR4 Antagonists for the Mobilization of Hematopoietic Stem and Progenitor Cells.

Author

Ruminski, Peter G., Rettig, Michael P., and DiPersio, John F.

Subjects
HEMATOPOIETIC stem cell transplantation, CELL receptors, STEM cell transplantation, HEMATOPOIETIC stem cells, PERIPHERAL circulation, CHEMOKINE receptors
Abstract

The treatment of patients diagnosed with hematologic malignancies typically includes hematopoietic stem cell transplantation (HSCT) as part of a therapeutic standard of care. The primary graft source of hematopoietic stem and progenitor cells (HSPCs) for HSCT is mobilized from the bone marrow into the peripheral blood of allogeneic donors or patients. More recently, these mobilized HSPCs have also been the source for gene editing strategies to treat diseases such as sickle-cell anemia. For a HSCT to be successful, it requires the infusion of a sufficient number of HSPCs that are capable of adequate homing to the bone marrow niche and the subsequent regeneration of stable trilineage hematopoiesis in a timely manner. Granulocyte-colony-stimulating factor (G-CSF) is currently the most frequently used agent for HSPC mobilization. However, it requires five or more daily infusions to produce an adequate number of HSPCs and the use of G-CSF alone often results in suboptimal stem cell yields in a significant number of patients. Furthermore, there are several undesirable side effects associated with G-CSF, and it is contraindicated for use in sickle-cell anemia patients, where it has been linked to serious vaso-occlusive and thrombotic events. The chemokine receptor CXCR4 and the cell surface integrin α4β1 (very late antigen 4 (VLA4)) are both involved in the homing and retention of HSPCs within the bone marrow microenvironment. Preclinical and/or clinical studies have shown that targeted disruption of the interaction of the CXCR4 or VLA4 receptors with their endogenous ligands within the bone marrow niche results in the rapid and reversible mobilization of HSPCs into the peripheral circulation and is synergistic when combined with G-CSF. In this review, we discuss the roles CXCR4 and VLA4 play in bone marrow homing and retention and will summarize more recent development of small-molecule CXCR4 and VLA4 inhibitors that, when combined, can synergistically improve the magnitude, quality and convenience of HSPC mobilization for stem cell transplantation and ex vivo gene therapy after the administration of just a single dose. This optimized regimen has the potential to afford a superior alternative to G-CSF for HSPC mobilization. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

47. CAR-modified memory-like NK cells exhibit potent responses to NK-resistant lymphomas

Author

Gang, Margery, Marin, Nancy D., Wong, Pamela, Neal, Carly C., Marsala, Lynne, Foster, Mark, Schappe, Timothy, Meng, Wei, Tran, Jennifer, Schaettler, Maximilian, Davila, Marco, Gao, Feng, Cashen, Amanda F., Bartlett, Nancy L., Mehta-Shah, Neha, Kahl, Brad S., Kim, Miriam Y., Cooper, Matthew L., DiPersio, John F., Berrien-Elliott, Melissa M., and Fehniger, Todd A.

Published
2020
Full Text
View/download PDF

48. TP53 abnormalities correlate with immune infiltration and associate with response to flotetuzumab immunotherapy in AML

Author

Vadakekolathu, Jayakumar, Lai, Catherine, Reeder, Stephen, Church, Sarah E., Hood, Tressa, Lourdusamy, Anbarasu, Rettig, Michael P., Aldoss, Ibrahim, Advani, Anjali S., Godwin, John, Wieduwilt, Matthew J., Arellano, Martha, Muth, John, Yau, Tung On, Ravandi, Farhad, Sweet, Kendra, Altmann, Heidi, Foulds, Gemma A., Stölzel, Friedrich, Middeke, Jan Moritz, Ciciarello, Marilena, Curti, Antonio, Valk, Peter J.M., Löwenberg, Bob, Gojo, Ivana, Bornhäuser, Martin, DiPersio, John F., Davidson-Moncada, Jan K., and Rutella, Sergio

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results