7 results on '"Amanda C. Przespolewski"'
Search Results
2. Targeting acute myeloid leukemia through multimodal immunotherapeutic approaches
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Scott Portwood, Amanda C. Przespolewski, and Eunice S. Wang
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Cancer Research ,Innate immune system ,business.industry ,medicine.medical_treatment ,Myeloid leukemia ,Hematology ,Immunotherapy ,medicine.disease ,Immunity, Innate ,Leukemia, Myeloid, Acute ,Mice ,Leukemia ,Immune system ,Oncology ,Interferon ,Apoptosis ,In vivo ,medicine ,Cancer research ,Animals ,Humans ,business ,medicine.drug - Abstract
Acute myeloid leukemia (AML) is an aggressive hematologic malignancy with a dismal prognosis. Immunotherapeutic approaches using single agent checkpoint inhibitors have thus far shown limited success. We hypothesized that successful adaptive anti-AML specific immune responses require additional modulation of innate immunity. DMXAA exposure resulted in modest apoptosis of C1498 AML cells with a subtle increase in PD-L1 expression and limited production of IL-6 and IFN-β. In contrast, DMXAA + anti-PD-1 ab, but not either agent alone, significantly decreased in vivo disease burden and prolonged overall survival in C1498 engrafted leukemic mice. Combination-treated mice demonstrated increased memory T-cells and mature dendritic cells, lower numbers of regulatory T-cells and evidence of leukemia apoptosis. Furthermore, these effects were associated with markedly increased serum levels of type I interferon (IFN) and IFN gamma. We demonstrate that combining an innate immune agonist with a checkpoint inhibitor synergistically improved anti-tumor activity in a preclinical AML model.
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- 2021
3. Low-level Cytomegalovirus Antigenemia Promotes Protective Cytomegalovirus Antigen Specific T-Cells after Allogeneic Hematopoietic Cell Transplantation
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Joseph D. Tario, Maureen Ross, Brahm H. Segal, Liselotte Brix, Theresa Hahn, Joanne Becker, Amanda C. Przespolewski, Yali Zhang, Philip L. McCarthy, George Chen, Marcie L. Riches, Nikolaos G. Almyroudis, and Paul K. Wallace
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medicine.medical_treatment ,T-Lymphocytes ,Congenital cytomegalovirus infection ,Cytomegalovirus ,Hematopoietic stem cell transplantation ,Major histocompatibility complex ,Article ,Immune system ,medicine ,Humans ,Transplantation, Homologous ,Prospective Studies ,Cmv antigenemia ,Transplantation ,biology ,Hematopoietic cell ,business.industry ,Hematopoietic Stem Cell Transplantation ,virus diseases ,Hematology ,medicine.disease ,Cytomegalovirus antigen ,Immunology ,Cytomegalovirus Infections ,biology.protein ,business - Abstract
Previous studies have reported a beneficial effect from CMV (cytomegalovirus) reactivation after alloHCT on immune reconstitution. We determined the CMV antigenemia level associated with increased CMV Antigen Specific T-cells (CASTs) at day+100 and decreased CMV reactivation after day+100. CMV reactivation and CASTs were measured with CMV antigenemia and CMV-specific major histocompatibility complex multimers. The analysis consisted of 775 CAST measurements obtained before and 30, 100, and 365 days post-alloHCT from 327 consecutive patients treated between 2008–2016. Detectable CASTs correlated with recipient (p
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- 2020
4. BITES and CARS and checkpoints, oh my! Updates regarding immunotherapy for myeloid malignancies from the 2018 annual ASH meeting
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Amanda C. Przespolewski and Elizabeth A. Griffiths
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Antigenicity ,medicine.medical_specialty ,Myeloid ,Immune checkpoint inhibitors ,medicine.medical_treatment ,Cancer Vaccines ,Immunotherapy, Adoptive ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,hemic and lymphatic diseases ,Antibodies, Bispecific ,medicine ,Animals ,Humans ,Immune Checkpoint Inhibitors ,Hematology ,biology ,business.industry ,Myeloid leukemia ,Immunotherapy ,Vaccine therapy ,Leukemia, Myeloid, Acute ,medicine.anatomical_structure ,Oncology ,Leukemia, Myeloid ,030220 oncology & carcinogenesis ,Myelodysplastic Syndromes ,biology.protein ,Cancer research ,Antibody ,business ,030215 immunology - Abstract
It is without question that immune checkpoint inhibitors and adoptive cellular therapies have revolutionized the treatment of solid and hematologic malignancies. Investigators are now developing novel strategies to integrate these groundbreaking modalities into the care of patients with acute myeloid leukemia (AML) and other myeloid malignancies. Here we provide an overview of the most recent developments in immunotherapy for myeloid cancers presented at the 2018 American Society of Hematology annual meeting. Topics discussed include adoptive cellular therapies (CAR-T, NK cell, and vaccines), checkpoint inhibitors, and bispecific T-cell engager (BITE) antibodies. Despite reservations regarding low antigenicity and having long been considered a "cold" tumor, immunotherapy remains a highly promising strategy for patients with aggressive myeloid cancers like myelodysplasia (MDS) and AML.
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- 2020
5. Malignancies in immune deficiencies
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Amanda C. Przespolewski, Brahm H. Segal, and Maya Khalil
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business.industry ,Hematopoietic stem cell ,Cancer ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Immunosurveillance ,Increased risk ,medicine.anatomical_structure ,Immune system ,Acquired immunodeficiency syndrome (AIDS) ,Cancer screening ,Immunology ,medicine ,bacteria ,Cancer development ,business - Abstract
It is recognized that certain primary immune deficiencies are associated with increased risk of specific pathogens and this has led to a greater understanding of the role of individual genes in mediating host defense against these pathogens. In a similar fashion, the increased risk of cancers associated with primary immune deficiencies provides us with insight about immune protections from malignancies. The immune system has the ability to identify and eradicate developing cancers, a phenomenon termed “cancer immunosurveillance” (Schumacher and Schreiber, 2015). The notion of the normal immune system preventing cancer development through immune surveillance is supported by the increased risk of cancers in immunocompromized patients, including persons with AIDS (Patel et al., 2008; Shiels et al., 2010; Shiels et al., 2011; Simard et al., 2010), hematopoietic stem cell transplant recipients (Majhail, 2011; Majhail et al., 2011), and solid organ transplant recipients (Engels et al., 2011). In these secondary immune deficiencies, multiple factors can influence the risk of cancer including impaired immunosurveillance as well as therapy-related genotoxicity (Olivero et al., 2007). In contrast, patients with primary immune deficiencies provide the opportunity to more directly delineate the role of immune protection from cancer at the level of specific genes and pathways. The goals of this chapter are to review immune deficient conditions in which the occurrence of cancer is strikingly high and describe the insights we gain regarding the role of the immune system in protecting from incident cancer. We will also discuss implications for cancer screening, gaps in knowledge, and future directions in research.
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- 2020
6. Contributors
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Michael S. Abers, Daria V. Babushok, Mark Ballow, Bertrand Boisson, Vincent Robert Bonagura, Francisco A. Bonilla, João Bosco de Oliveira Filho, Kaan Boztug, Lori Broderick, Manish J. Butte, Fabio Candotti, Jean-Laurent Casanova, Shanmuganathan Chandrakasan, Antonio Condino-Neto, Yanick J. Crow, Charlotte Cunningham-Rundles, Virgil A.S.H. Dalm, Adriana A. de Jesus, Emma de Maio, Geneviève de Saint Basile, Esther de Vries, Inderjeet Dokal, Christopher J.A. Duncan, A. Durandy, Stephan Ehl, Amos Etzioni, Polly J. Ferguson, Thomas A. Fleisher, Lisa R. Forbes-Satter, Michael M. Frank, Alexandra F. Freeman, Marie-Louise Frémond, John W. Frew, Mathieu Fusaro, Eleonora Gambineri, Rebecca D. Ganetzky, Andrew R. Gennery, Raphaela Goldbach-Mansky, Amy C. Goldstein, John M. Graham, Stephanie E. Gupton, Elie Haddad, Sophie Hambleton, Eric P. Hanson, Jennifer Heimall, Miep Helfrich, Sarah E. Henrickson, Steven M. Holland, Amy P. Hsu, Soma Jyonouchi, Sara Kashef, Judith Kelsen, Maya Khalil, Christoph Klein, Lisa Kobrynski, Donald B. Kohn, S. Kracker, James G. Krueger, Pascal M. Lavoie, Heather K. Lehman, Jennifer W. Leiding, Michael J. Lenardo, Ofer Levy, Allison Pecha Lim, Michail S. Lionakis, Andrea Lisco, Vassilios Lougaris, Saul O. Lugo Reyes, M. Louise Markert, Rebecca A. Marsh, Elizabeth A. McCarthy, Isabelle Meyts, Cinzia Milito, Joshua D. Milner, Jeffrey E. Ming, Despina Moshous, Ludmila Müller, Kristina Navrazhina, Kim E. Nichols, Luigi D. Notarangelo, Eric Oksenhendler, Jordan S. Orange, Roberto Paganelli, Graham Pawelec, Tancredi Massimo Pentimalli, Elena E. Perez, Capucine Picard, Alessandro Plebani, Oscar Porras, Amanda C. Przespolewski, Anne Puel, Federica Pulvirenti, Isabella Quinti, Nima Rezaei, Ger T. Rijkers, David Walter Rosenthal, Sergio D. Rosenzweig, Brahm H. Segal, Mikko R.J. Seppänen, Irini Sereti, Anna Shcherbina, Cristina Sobacchi, Jacqueline D. Squire, Polina Stepensky, Helen C. Su, Kathleen E. Sullivan, Troy R. Torgerson, Gulbu Uzel, Mirjam van der Burg, Anna Villa, Jean-Pierre de Villartay, Klaus Warnatz, Richard L. Wasserman, Corry M.R. Weemaes, Joyce E. Yu, Shen-Ying Zhang, and John B. Ziegler
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- 2020
7. Safety and efficacy of CPX-351 in younger patients < 60 years old with secondary acute myeloid leukemia: An updated analysis
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Kendra Sweet, Eunice S. Wang, Salman Fazal, Chetasi Talati, Swapna Thota, Amanda C. Przespolewski, James E. Thompson, Elizabeth A. Griffiths, Jeffrey Baron, Srinivasa R. Sanikommu, and Pankit Vachhani
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Induction chemotherapy ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Secondary Acute Myeloid Leukemia ,business ,030215 immunology - Abstract
e18530 Background: Patients (pts) with secondary acute myeloid leukemia (s-AML) have poor long-term outcomes following standard induction chemotherapy with 7+3. In 2017 CPX-351 was FDA approved for upfront treatment of s-AML. The phase 3 trial demonstrated improved overall survival in pts aged 60-75 years old. Although CPX-351 treatment is indicated in all adults with s-AML, it is unclear whether CPX-351 is safe and effective in younger pts < 60 years. We sought to address this unanswered question by retrospective review of clinical experience since FDA approval. Methods: Medical records were retrospectively reviewed at five large academic centers to identify pts aged 18-59 years old with untreated s-AML, prior cytotoxic therapy, or AML-MRC treated with CPX-351 as induction therapy. Results: 30 pts with confirmed s-AML received CPX-351 therapy. Mean age was 53 years (range 23 – 59), 18 were male (60%). The majority (60%, N = 18) had AML-MRC, 7 (23%) had treatment-related AML (t-AML) and 6 (20%) had antecedent MDS. 6 pts had received prior HMA therapy. 19 pts had a complex karyotype (70%), and 4 patients were found to have a normal karyotype (15%). The most common molecular event was TP53 mutation observed in 10 pts (36%), followed by FLT3-ITD identified in 4 pts (14%). Overall response rate (CR/CRi/PR) was 46.7% with 5 CR (17.2%), 3 CRi (10.3%), and 6 PR (20.7%). The remaining pts (15/29, 51.7%) were non-responders. 8 pts have received an allogenic stem cell transplant. The most common AE was infection (80%, 24/30) with 4 clinically significant bleeding events. Thirty-day mortality was 13.3%, with 60-day mortality of 16.7%. Overall survival was 7 months (range 0.5 – 12.4 months), with mean follow up of 4.4 months. Conclusions: This multi-institutional retrospective analysis suggests that CPX-351 results in lower response rates (CR/CRi 27.6%) and shorter overall survival (7 mos) than reported in the recently published phase 3 trial in pts aged 60-75 years old. Potential explanations for this discrepancy include short follow up, small sample size, retrospective design, and the significant proportions of pts with complex karyotype and TP53 mutations. Historically, patients < 65 years old with s-AML have had a reported overall survival of approximately 7 months. Further investigation of this regimen in younger pts with s-AML as compared with 7+3 and other approaches is warranted.
- Published
- 2019
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