Cancer Cell. 2021 Jun 29. PMID: 34242572
This is the first study to analyze a large number (320) of patients with multiple myeloma (MM) after completing two doses of mRNA COVID-19 vaccines and compare their SARS-CoV-2 spike-binding IgG antibody response to a control group of healthy patients. Findings showed that the patients with MM mounted suboptimal and variable antibody responses. Patients who had not contracted COVID-19 before being vaccinated were more likely to have delayed and suboptimal vaccine responses, and patients undergoing active treatment for their MM had significantly lower antibody levels; 15.8% developed no detectable antibodies. These findings underscore the importance of routine serological monitoring of MM patients following vaccination to allow for personalized risk reduction measures. Studies to determine virus neutralization, IgG subtype, and T cell immunity—needed to fully understand COVID-19-vaccine-induced immune responses in MM patients—are ongoing.
All Authors: Oliver Van Oekelen, Charles R. Gleason, Sarita Agte, Komal Srivastava, Katherine F. Beach, Adolfo Aleman, Katerina Kappes, PVI/Seronet team, Tarek H. Mouhieddine, Bo Wang, Ajai Chari, Carlos Cordon-Cardo, Florian Krammer, Sundar Jagannath, Viviana Simon; Ania Wajnberg, Samir Parekh
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Center of Excellence for Liver and Bile Duct Cancer |
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The Center of Excellence (COE) for Liver and Bile Duct Cancer, under the leadership of Myron Schwartz, MD, is the most recently launched cancer center of excellence at The Tisch Cancer Institute. The COE for Liver and Bile Duct Cancer is the largest liver cancer program in the United States, with more than 400 new patients each year who have cancer that started in the liver.
Research Laboratories at the COE for Liver and Bile Duct Cancer:
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The laboratory of Ernesto Guccione, PhD, explores weaknesses in cancer cells. Dr. Guccione uses organoids—miniature livers created in the laboratory from tissue samples removed during biopsies or surgery—to test new drugs and other treatments.
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Links to all of the cancer centers of excellence can be found on
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Douglas Tremblay, MD, has joined the faculty as Assistant Professor of Medicine (Hematology and Medical Oncology). Dr. Tremblay completed fellowship and residency training at Mount Sinai and served as both Chief Fellow and Chief Resident. He earned his MD at Albert Einstein College of Medicine. Dr. Tremblay will see patients at the Ruttenberg Treatment Center. His clinical and translational research focus is on hematologic malignancies, particularly acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), and myelodysplastic/myeloproliferative overlap syndromes. Dr. Tremblay is leading several interdisciplinary projects and is developing investigator-initiated protocols in myeloid neoplasms. He has more than 60 peer-reviewed publications.
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Elena Grossi, PhD, postdoctoral fellow in Emily Bernstein’s laboratory, was awarded grant funding from the National Cancer Center for “Profiling SWI/SNF complex mutations in melanoma initiation.” In this project, Dr. Grossi aims to employ a novel gene-editing technology to model melanoma-relevant SWI/SNF mutations, explore the consequences of mutant complexes by integrating functional studies with epigenomic and transcriptomic profiling, and elucidate the epigenetic mechanisms by which mutant SWI/SNF components promote melanoma initiation. The ultimate goal is to translate these findings to clinically relevant models.
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Eirini Papapetrou, MD, PhD, has received grant funding from the Edward P. Evans Foundation for “The role of mutations in epigenetic regulators in the pathogenesis of MDS.” The aim of this project is to study cell-intrinsic and cell-extrinsic effects of the three most common clonal hematopoiesis (CH) mutations that affect genes regulating the epigenome: DNMT3A, TET2, and ASXL1. In addition, using innovative genetically engineered iPSC models, Dr. Papapetrou and team will test the dependency of fully transformed leukemia cells upon the initiating epigenetic CH mutation. Study findings may lead to identification of biomarkers that can be used to monitor individuals with CH, inform risk estimates of progression to myeloid malignancy and other morbidities in order to derive effective guidelines for the monitoring and counseling of patients, and ultimately, prevent MDS and AML development.
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Arvin Dar, PhD, was awarded a R01 grant from the National Cancer Institute for “A chemical genetic approach to exploring novel therapeutic space for colorectal cancer.” The project will use a multidisciplinary approach for accessing novel target and chemical space to derive highly precise polypharmacological drugs. Combining chemical and genetic modifier screens with computational modelling will enable identification of distinct kinases that can strongly enhance or limit the activity of kinase inhibitors within models of KRAS variant metastatic colorectal cancer. The researchers can then harness the information to predict and synthesize novel compounds optimized toward whole animal networks. Ross Cagan, PhD, formerly at Mount Sinai and now at the University of Glasgow, is Multiple Principal Investigator on the grant.
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Alice Kamphorst, PhD, was awarded a R01 grant from the National Institute of Allergy and Infectious Diseases for “Determinants of differentiation and maintenance of PD-1+ CD8 T cells.” Using a mouse model of chronic viral infection, Dr. Kamphorst and team will study how co-stimulation and cellular interactions shape the maintenance and function of PD-1+ CD8 T cell responses. The knowledge gained will be critical for understanding fate decisions by chronically stimulated CD8 T cells and improving immune interventions.
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Qin Yu, PhD, received a Department of Defense Kidney Cancer Research Program award for “Targeting the shedding of transmembrane PD-L1 to enhance therapeutic efficacy of immune checkpoint inhibitors.” The aim of the project is to improve understanding of the regulatory mechanisms of the ligands of immune checkpoint proteins. This will enable Dr. Yu to establish the base for sensitizing the response of renal cell carcinoma to lower and safer doses of immune checkpoint inhibitors by targeting the shedding of PD-L1 that results in more potent soluble PD-L1. |
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Arvin Dar, PhD, Ernesto Guccione, PhD, and Amaia Lujambio, PhD, are Co-Principal Investigators on a newly awarded R01 grant from the National Cancer Institute: “An integrated platform for novel personalized liver cancer therapeutics.” In this project, the researchers’ laboratories will advance a multidisciplinary drug development platform that utilizes precision mouse models, tumor 3D organoids, and a proprietary library of small molecule inhibitors as a launching point to uncover novel biological targets for precision-based therapeutics in hepatocellular carcinoma. They have already identified a strong lead which they are referring to as WNTinib, based on the ability of the compound to antagonize the growth of tumors with alterations in the WNT pathway component CTNNB1. This grant will support further development of WNTinib along with secondary hits from screens.
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Deadline: August 25, 2021
Amount/Duration: Up to $1 million over three years
The Health Equity SU2C Catalyst Team must include clinical and health economic expertise, including senior and early‐career investigators who have not worked together in the past, with a minimum of three participating institutions.
The TCI Development team can assist with this grant application. Contact Lauren Walker (Lauren.Walker@mountsinai.org) for additional information.
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Keith Sigel, MD, is the Study Chair on a new national study that will evaluate the feasibility of using a smartphone-based application designed to help people living with HIV to quit smoking. Individuals with HIV who smoke are especially vulnerable to lung cancer. Sponsored by the National Cancer Institute (NCI) and conducted via the AIDS Malignancy Consortium, the study will collect data on this novel smoking cessation tool, which will be delivered at the time of low dose computed tomography lung cancer screening and that may serve as a key component of the lung cancer screening process. The study will also collect information on the utility of lung cancer screening for people with HIV. The smartphone application was designed in a previous NCI-funded study by Jonathan Shuter, MD at Albert Einstein College of Medicine. The study is expected to enroll 100 participants, starting later in 2021. |
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Sacha Gnjatic, PhD, presented “Profiling multiple myeloma using antigen-specific and high-dimensional immune monitoring” at the 13th Annual Meeting of the Japanese Society of Immunotherapy for Hematological Disorders, held in June. Program
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The Division of Hematology and Medical Oncology welcomes eight new first year fellows.
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Click here for the roster.
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All fellows are listed here.
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In other fellowship news, Teja Ganta, MD, third-year fellow, is finishing an integrated fellowship experience that combines both Hematology and Medical Oncology and Clinical Informatics training. He will be the first fellow completing this new combined fellowship pathway, and will be eligible for board exams in all three specialties. The combined training will enable Dr. Ganta to excel as a cancer physician and clinical informaticist, and lead innovations in artificial intelligence/machine learning, health information systems, and digital medicine. This novel fellowship pathway was designed under the guidance of Adriana Malone, MD, Director of the Hematology and Medical Oncology Fellowship Program, and Joseph Kannry, MD, Director of the Clinical Informatics Fellowship Program.
Dr. Ganta was recently accepted to the National Cancer Institute’s DataViz + Cancer Innovation Lab. Developed as part of the Cancer Moonshot, the lab is “intended to catalyze unconventional, interdisciplinary teams involving game designers, patient advocates, clinicians, and researchers to spur novel ideas around designing for a more patient-centered experience.”
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Maria Soledad Sosa, PhD, is one of two recipients of the inaugural Exceptional Scholar Award from the Icahn School of Medicine at Mount Sinai, sponsored by the Institute for Health Equity Research. Assistant professors from diverse backgrounds with independent research programs were eligible to apply.
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bioRxiv. 2021 Jul 14 (PREPRINT)
This paper reports on a new technology—called Perturb-map—which enables the first spatial functional genomic analysis of the tumor microenvironment (TME). The platform enables CRISPR genomics with spatial resolution in tissue sections. In the study, the researchers leveraged Pertub-map to study how cytokine signaling in cancer cells regulates the architecture and immune composition of the TME. They discovered that loss of the TGF beta receptor (TGFBR2) leads to remodeling of the lung tumor microenvironment and exclusion of T cells from the tumor, which resulted from increased TGFb signaling in the tumor stroma. This provides new insight on how Tgfbr2 loss can affect loss of cancer control. Findings establish Perturb-map for functional genomics within a tissue at single cell-resolution with spatial architecture preserved.
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Nature. 2021 Jun 16. PMID: 34135508
Researchers discovered that early-stage lung cancer tumors coopt immune cells, known as tissue-resident macrophages, to help invade lung tissue. They identified the process of how the macrophages enable a tumor to invade the tissues the macrophages normally repair—and they also showed that the macrophages also turn off antitumor T cell function. The findings will aid in the development of immunoprevention strategies to disarm tumor progression in patients at risk by either deletion or reprogramming macrophages to promote antitumorigenic function.
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Clinical Cancer Research. 2021 Jul 12. PMID: 34253580
The Cancer Immune Monitoring and Analysis Centers - Cancer Immunologic Data Commons (CIMAC-CIDC) network supported by the NCI Cancer Moonshot initiative provides correlative analyses for clinical trials in cancer immunotherapy. Multiplex immunohistochemical assays are used to define the composition and distribution of immune infiltrates within tumors in the context of their potential role as biomarkers. Results based on data generated at three CIMAC sites confirm that CIMAC-CIDC analyses may be used with confidence for statistical associations with clinical outcomes largely independent of site, antibody selection, protocol, and platform across different sites.
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Journal of Clinical Oncology. 2021 Jun 17. PMID: 34138638
This paper reports on results of a phase II study of imetelstat, a telomerase inhibitor, for patients with myelofibrosis who are relapsed or refractory to Janus-associated kinase inhibitors (JAKis). Imetelstat demonstrated clinical benefit and potential disease-modifying activity with an acceptable safety profile, suggesting that it may be a viable treatment option.
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In this review, the authors discuss the molecular basis of targeted protein degradation (TPD), provide a comprehensive account of the most promising degraders in preclinical and clinical development as cancer therapies, and offer insights for further advancing the TPD field.
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PLoS Genetics. 2021 Jun 24. PMID: 34166362
This study was designed to identify novel drivers of hepatocellular carcinoma (HCC) tumor progression from low-grade tumors to high-grade, aggressive malignancies. Findings revealed that one family of genes—cancer testis antigens (CTAs)—was recurrently over-expressed in the most aggressive regions of the tumors and that X-chromosome located CTAs, and especially MAGEA3, are associated with markers of poor prognosis. Selective inhibition of MAGEA3 has antitumor activity in experimental models of HCC, which supports its evaluation as a novel therapeutic target in HCC.
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Clinical Cancer Research. 2021 Jun 22. PMID: 34158358
This paper reports on the discovery of three structurally related compounds (SOX11i) that bind SOX11—a transcription factor overexpressed in the majority of mantle cell lymphoma (MCL)—perturb its interaction with DNA, and effect SOX11-specific antiMCL cytotoxicity. The findings provide a foundation for therapeutically targeting SOX11 in MCL by a novel class of small molecules.
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Nature Communications. 2021 Jun 29. PMID: 34188055
PrimPol is a human DNA polymerase-primase that localizes to mitochondria and nucleus and bypasses the major oxidative DNA lesion (8-oxoG) formed in cells. The authors provide structural insights into how PrimPol performs accurate translesion synthesis opposite such oxidatively damaged DNA in human cells.
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Philipp Haber, MD; Marc Puigvehi, PhD; Vennis Lourdusamy; Michael Buckstein, MD, PhD; Parissa Tabrizian, MD; Edward Kim, MD; Augusto Villanueva, MD, PhD; Myron Schwartz, MD; Josep Llovet, MD; et al.
Gastroenterology. 2021 Jun 11. PMID: 34126063
This paper reports on a systematic review of 49 high-quality phase III randomized controlled trials including a total of 22,113 patients across disease states. Meta-analysis designed to examine the relationship between etiology and outcome after systemic therapies with either tyrosine-kinase inhibitor/antiangiogenic or immune checkpoint inhibitors therapy showed that immunotherapies may be less effective in non-viral etiologies.
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You can help TCI create a robust schedule of invited speakers for 2021-2011.
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Do you have news for the next issue of TCI Connections?
Please send to Janet Aronson (646-745-6376).
Remember to share breaking news and high impact news that might be appropriate for media coverage with Marlene Naanes (929-237-5802) in the Press Office. This may include pending FDA drug/device approvals, studies/trial results being published in high-impact journals, and patient stories. The more lead time you can give Marlene, the better—ideally, four weeks or when a paper is accepted by the journal. Embargoes will always be honored and news will only be released with your approval.
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Ramon Parsons, MD, PhD, Director
Janet Aronson , Editor
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