Jonathan E Cohen

Jonathan E Cohen
Hadassah Medical Center | hadassah · Sharett Institute of Oncology

MD, PhD

About

73
Publications
7,483
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1,116
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Introduction
I am a physician-researcher and head of clinical research at the Sharett Institute of Oncology. I am a senior medical oncologist, specializing in melanoma and cancer immunotherapy and also a member of the gastro-intestinal medical oncology team. My research focuses on cancer immunotherapy.

Publications

Publications (73)
Article
In the adult murine hippocampus, dentate gyrus (DG), neurogenesis and neural cell death are thought to affect learning and memory in incompletely understood mechanism(s). Because cholinergic neurotransmission influences both of these functions, we hypothesized that cholinergic signaling, affected by acetylcholinesterase (AChE) activity, expression...
Article
Patients with post-traumatic stress disorder (PTSD) suffer from a failure of cognitive control over emotional distracters. The physiological substrates of cognitive-emotional interactions and their breakdown in disease are, however, unknown. Here, we studied brain activity in PTSD patients and healthy controls in response to emotion-provoking pictu...
Article
The immune system is a potent inhibitor of tumor growth with curative potential, constituting in many eyes the future of antineoplastic therapy. Adoptive cell therapy (ACT) is a form of immunotherapy in which autologous cancer-cognate lymphocytes are expanded and modified ex vivo and re-infused to combat the tumor. This review follows the evolvemen...
Article
Full-text available
Melanoma survival increased with targeted- and immunotherapy agents, yet most patients ultimately progress and require salvage therapy. In our experience, some progressive disease patients on immune-checkpoint inhibitors (ICIs) demonstrate deep and sustained responses to chemotherapy. We hypothesized that ICIs improve the response to subsequent che...
Article
Full-text available
A Correction to this paper has been published: https://doi.org/10.1038/s41587-021-00831-9.
Article
258 Background: Telisotuzumab adizutecan is an antibody-drug conjugate comprising the c-Met–targeting antibody telisotuzumab conjugated to a topoisomerase 1 inhibitor payload, adizutecan. A phase 1 trial (NCT05029882) in advanced solid tumors reported higher response rates in pts with CRC and high c-Met expression. We present an analysis of respons...
Article
490 Background: c-Met protein (MET protein) overexpression (OE) and MET amplification (amp) occur in several cancer types, including GEA, and are associated with poor prognosis. The c-Met–directed antibody-drug conjugate telisotuzumab adizutecan (ABBV-400) is being assessed in advanced solid tumors in an ongoing, first-in-human study (NCT05029882)....
Article
Full-text available
Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB–D melanoma. Here we report results from the first three arms: pe...
Conference Paper
Full-text available
Background SAR444881, a first-in-class humanized immunoglobulin (Ig) G4 monoclonal antibody (mAb) selectively binds to inhibitory receptor Ig-like transcript 2 (ILT2) on NK/T cells/macrophages, blocking its interaction with major histocompatibility complex class I. Preclinical studies showed that SAR444881±anti-PD-1 or EGFR mAbs enhanced antitumor...
Article
3515 Background: c-Met (MET protein) is frequently overexpressed in several advanced solid tumors including colorectal cancer (CRC). There are no approved therapies specific for c-Met–overexpressing tumors in CRC. The antibody-drug conjugate ABBV-400 comprises c-Met–targeting antibody telisotuzumab conjugated to a novel topoisomerase 1 inhibitor pa...
Article
4139 Background: Standard first-line treatment of mPDAC includes Gem/Nab-P doublet therapy, which typically results in an ORR of 23%-35%, a median PFS of 5-6 mo, and a median OS of 7-10 mo. ILT3 is an inhibitory receptor expressed on monocytic myeloid cells, including tolerogenic dendritic cells and myeloid-derived suppressor cells. MK-0482 is a no...
Article
9506 Background: Anti–PD-(L)1–refractory melanoma is a major challenge, and immunotherapy combination treatment may be useful in this patient population. The phase 1/2 KEYMAKER-U02A (NCT04305041) is a multi-arm, open-label, adaptive umbrella study designed to evaluate pembro + investigational agents for the treatment of anti–PD-(L)1–refractory mela...
Article
Full-text available
Background Radiotherapy has an important role in the treatment of brain metastases but carries risk of short and/or long-term toxicity, termed radiation-induced brain injury (RBI). As the diagnosis of RBI is crucial for correct patient management, there is an unmet need for reliable biomarkers for RBI. The aim of this proof-of concept study is to d...
Article
TPS9611 Background: Pembrolizumab is an anti−PD-1 monoclonal antibody that has been shown to significantly improve recurrence-free survival and distant metastasis-free survival when used as adjuvant therapy in patients with high-risk resected melanoma (Long GV, et al. Lancet Oncol. 2022;23:1378-88; Eggermont AMM, et al. Lancet Oncol. 2021;22:643-54...
Article
Background: The phase 1/2 KEYMAKER-U02 substudy 02C (NCT04303169) is evaluating neoadjuvant pembro + investigational agents or pembro alone followed by adjuvant pembro in stage IIIB-D melanoma. Results from patients treated with neoadjuvant pembro (anti-PD-1) + vibo (anti-TIGIT; arm 1), pembro + geba (coxsackievirus A21; arm 2), or pembro alone (ar...
Preprint
Full-text available
Radiotherapy has an important role in the treatment of brain metastases (BrM) but carries risk of short and/or long-term toxicity, termed radiation-induced neurotoxicity (RIN). As the diagnosis of RIN is crucial for correct pa-tient management, there is an unmet need for reliable biomarkers for RIN. The aim of this proof-of concept study was to det...
Article
Full-text available
Objectives Traumatic stress has been associated with increased risk for brain alterations and development of anxiety disorders. Studies conducted in posttraumatic patients have shown white‐mater volume and diffusion alterations in the corpus‐callosum. Decreased cognitive performance has been demonstrated in acute stress disorder and posttraumatic p...
Article
Full-text available
The analysis of cell-free DNA (cfDNA) in plasma provides information on pathological processes in the body. Blood cfDNA is in the form of nucleosomes, which maintain their tissue- and cancer-specific epigenetic state. We developed a single-molecule multiparametric assay to comprehensively profile the epigenetics of plasma-isolated nucleosomes (EPIN...
Article
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Immune checkpoint receptors (ICR) modulate the immune response and are critical hubs for immunotherapy. However, data on their role in T lymphoid malignancies, such as cutaneous T cell lymphoma (CTCL), is sparse. We aimed to explore the role of ICR in the malignant features of transformed T lymphocytes and evaluate the effect of ICR-targeting monoc...
Preprint
Small cell lung cancer (SCLC) is an aggressive malignancy with exceptionally poor prognosis and limited therapeutic advances in the past few decades. Although SCLCs are treated as a single disease entity in clinic, emerging data support subtypes of SCLC driven by expression of distinct transcription regulators, which engender unique therapeutic vul...
Article
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Cancer inflicts damage to surrounding normal tissues, which can culminate in fatal organ failure. Here, we demonstrate that cell death in organs affected by cancer can be detected by tissue-specific methylation patterns of circulating cell-free DNA (cfDNA). We detected elevated levels of hepatocyte-derived cfDNA in the plasma of patients with liver...
Article
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BACKGROUND Brain radiotherapy is the main therapeutic modality for brain metastases (BM), but carries short and long term toxicities, termed radiation-induced neurotoxicity (RIN), and classified to acute, early-delayed and late-delayed RIN according to its time onset. Although diagnosis of RIN is crucial for patient management, there is an unmet ne...
Preprint
Full-text available
The analysis of cell-free DNA (cfDNA) in plasma represents a rapidly advancing field in medicine, providing information on pathological processes in the body. Blood cfDNA is in the form of nucleosomes, which maintain their tissue- and cancer-specific epigenetic state. We developed EPINUC, a single-molecule multi-parametric assay to comprehensively...
Article
Full-text available
Background LY3022855 is a recombinant, immunoglobulin, human monoclonal antibody targeting the colony-stimulating factor-1 receptor. This phase 1 trial determined the safety, pharmacokinetics, and antitumor activity of LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid cancers who had received standard anti-can...
Article
Full-text available
Cell-free DNA (cfDNA) in human plasma provides access to molecular information about the pathological processes in the organs or tumors from which it originates. These DNA fragments are derived from fragmented chromatin in dying cells and retain some of the cell-of-origin histone modifications. In this study, we applied chromatin immunoprecipitatio...
Article
Full-text available
A Correction to this paper has been published: https://doi.org/10.1038/s41587-021-00853-3.
Article
SLAMF6 is a homotypic receptor of the Ig-superfamily associated with progenitor exhausted T cells. Here we show that in humans, SLAMF6 has three splice isoforms involving its V-domain. Although the canonical receptor inhibited T-cell activation through SAP recruitment, the short isoform SLAMF6∆17-65 had a strong agonistic effect. The costimulatory...
Preprint
SLAMF6 is a homotypic receptor of the Ig-superfamily associated with progenitor exhausted T cells. In humans, SLAMF6 has three splice isoforms involving its V-domain. While the canonical 8-exon receptor inhibits T cell activation through SAP recruitment, the short isoform SLAMF6Δ17-65 has a strong agonistic effect. The costimulatory action depends...
Article
Full-text available
Objective The aim of this study was to investigate if the treatment outcomes of checkpoint inhibitors (CPI) in patients with advanced-stage skin head and neck melanoma (HNM) differs from outcomes in patients with non-HNM. Design A retrospective cohort study of patients with unresectable AJCC stage III and stage IV, who received CPI between 2010 an...
Article
Full-text available
SLAMF6 is a homotypic receptor of the Ig-superfamily whose exact role in immune modulation has remained elusive. Its constitutive expression on resting and activated T cells precludes it from being a bona fide exhaustion marker. By breeding Pmel-1 mice with SLAMF6 -/- mice, we generated donors for T cells lacking SLAMF6 and expressing a transgenic...
Preprint
Full-text available
SLAMF6 is a homotypic receptor of the Ig-superfamily whose exact role in immune modulation has remained elusive. Its constitutive expression on resting and activated T cells precludes it from being a bona fide exhaustion marker. By breeding Pmel-1 mice with SLAMF6 KO mice, we generated donors for T cells lacking SLAMF6 and expressing a transgenic T...
Article
Advances in the treatment of metastatic melanoma have improved responses and survival. However, many patients continue to experience resistance or toxicity to treatment, highlighting a crucial need to identify biomarkers and understand mechanisms of response and toxicity. Neoadjuvant therapy for regional metastases might improve operability and cli...
Article
INTRODUCTION Radiotherapy is a common treatment for brain metastases. However, it is commonly associated with central nervous system (CNS) toxicity. There are no biomarkers for early detection of radiotoxicity. Here we explore the utility of cell-free circulating DNA (cfDNA) for detection of brain cells death in the context of brain metastases. Usi...
Article
Background Radiotherapy is a common treatment for brain metastases. However, it is commonly associated with central nervous system (CNS) toxicity, leading to functional disability. There are no biomarkers capable of detecting preclinical neurotoxicity for the purpose of early detection of radiation-induced CNS damage. Here we explore the utility of...
Article
Full-text available
Leiomyosarcoma is the second most frequent soft-tissue sarcoma. Tumor lymphocytic infiltration (TIL) and programed cell death ligand-1 (PD-L1) have been associated with prognosis in different malignancies while DNA mismatch-repair deficiency (MMR-D) has been associated with response to check-point inhibitors. In this pilot study, we sought to exami...
Article
CD8 lymphocytes are mandatory mediators of tumor regression. To enhance their specific antitumor activity, we aimed to improve a melanoma cell-based vaccine by transfecting it with 4-1BB ligand, a costimulatory and immune modulatory molecule. Thirty-four American Joint Committee on Cancer (AJCC) stage IIB–IV patients were vaccinated with a melanoma...
Article
Full-text available
Altered brain anatomy in specific gray-matter regions has been shown in patients with posttraumatic stress disorder (PTSD). Recently, white-matter tracts have become a focus of research in PTSD. The corpus callosum (CC) is the principal white-matter fiber bundle, crucial in relaying sensory, motor and cognitive information between hemispheres. Alte...
Data
Complete Data Set used for data analysis in the current study. (ZIP)
Article
Full-text available
Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophe...
Article
Background: Predictive biomarkers for personalized treatment of neoplasms are suggested to be a major advancement in oncology and are increasingly used in clinical practice, albeit based on level II evidence. Target Now®(TN) employs immunostaining and RNA expression on tumor samples to identify potentially beneficial or ineffective drugs. Objective...
Article
Patients with posttraumatic stress disorder (PTSD) display abnormal emotional processing and bias towards emotional content. Most neurophysiological studies in PTSD found higher amplitudes of event-related potentials (ERPs) in response to trauma-related visual content. Here we aimed to characterize brain electrical activity in PTSD subjects in resp...
Conference Paper
Full-text available
Background: Gray-matter volume loss (e.g., in the hippocampus and amygdala) are frequently reported in posttraumatic-stress disorder (PTSD). Recently, studies have highlighted white-matter alterations as potentially involved in PTSD symptomatology. While these studies show promise for further characterization of PTSD-related abnormalities, most cri...
Conference Paper
Posttraumatic stress disorder (PTSD) patients display abnormal emotional processing and bias towards negative emotional content. In the current study we aimed to test the hypothesis that abnormal emotional responsiveness in PTSD is reflected in altered brain electrical activity, as measured via event-related potentials (ERPs). ERPs were recorded fr...
Article
Memory deficits are a common complaint of patients with posttraumatic stress disorder (PTSD). Despite vivid trauma-related memory, previous studies report memory impairment for nontrauma-related stimuli when compared to controls, specifically in associative memory (Guez et al., 2011). Healthy individuals show hemispheric memory asymmetry with left-...
Conference Paper
Full-text available
Memory deficits are a common complaint of patients with post-traumatic stress disorder (PTSD). Notably, alongside their persistent personal traumatic memory, traumatized patients may be impaired not only in remembering aspects of the trauma/fear-related stimuli but also in non-trauma related memory, with studies reporting a robust impairment in mem...
Article
e21508 Background: Pazopanib (P) is a multikinase inhibitor targeting the VEGF and PDGF receptors capable of controlling soft tissue sarcoma for several months. Acquired resistance to P usually leads to chemotherapy resumption. We present a case of reversal of acquired resistance to P by addition of an mTOR inhibitor. Methods: A 46 year old female,...
Conference Paper
Background: Memory deficits are a common complaint reported by patients with post-traumatic stress disorder (PTSD). Despite their vivid trauma-related memory, studies confirmed memory impairment for non-trauma related stimuli when compared to controls; specifically in associative memory (Guez et al., 2011). Studies in healthy individuals showed hem...
Conference Paper
Full-text available
Memory deficits are a common complaint reported by posttraumatic stress disorder (PTSD) patients. Despite their vivid trauma-related memory, studies in PTSD patients confirmed memory impairment for non-trauma related stimuli when compared to controls; specifically in associative memory. Magnetic resonance imaging (MRI) studies in PTSD patients have...
Article
Full-text available
Post-traumatic anxiety notably involves inflammation, but its causes and functional significance are yet unclear. Here, we report that failure of the innate immune system Toll-like receptor 9 (TLR9) to limit inflammation is causally involved with anxiety-associated inflammation and that peripheral administration of specific oligonucleotide activato...
Article
Full-text available
Individuals with posttraumatic stress disorder (PTSD) are haunted by persistent memories of the trauma, but ironically are impaired in memories of daily life. The current set of 4 experiments compared new learning and memory of emotionally neutral content in 2 groups of patients and aged- and education-matched controls: 20 patients diagnosed with c...
Chapter
IntroductionGenetic Polymorphisms Contributing to Anti-ChE SensitivityConclusion References
Chapter
IntroductionSerotoninAdrenergic Antagonistsγ-Aminobutyric AcidSummaryReferences
Article
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Long-lasting alternative splicing of neuronal acetylcholinesterase (AChE) pre-mRNA occurs during neuronal development and following stress, altering synaptic properties. To explore the corresponding molecular events, we sought to identify mRNAs encoding for abundant splicing factors in the prefrontal cortex (PFC) following stress. Here we show elev...

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