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Mashup Score: 13Systematic review of immune checkpoint inhibitor-related gastrointestinal, hepatobiliary, and pancreatic adverse events - 7 day(s) ago
Gastrointestinal immune-related adverse events (GI irAEs) are common manifestations of immune checkpoint inhibitor (ICI) toxicity. We present a comprehensive systematic review of the incidence, management, and clinical course of irAEs across the entire GI system, including the luminal GI tract, liver, and pancreas. MEDLINE, Embase, Web of Science Core Collection, and Cochrane Library were used to conduct this review. All studies pertaining to GI irAEs were included. Both abstracts and full manuscripts were eligible if they included human subjects and were written in the English language. Articles not available in English, animal studies, or research not specific to GI toxicity of immunotherapy were excluded. We excluded certain article types depending on whether stronger evidence was available in the literature for a specific toxicity, for example, if prospective studies were available on a topic, retrospective studies and case reports were excluded. We extracted a final 166 articles f
Source: jitc.bmj.comCategories: General Medicine News, Hem/OncsTweet
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Mashup Score: 120
Background The association between safety and efficacy of immune checkpoint inhibitors is known, but the correlation between severity and impact of specific organ involvement by immune-related adverse events (irAE) and cancer outcomes is poorly understood. Most irAEs are mild-to-moderate but severe irAEs may pose clinical management challenges and affect patient outcomes. Methods We assessed the association between irAE grade (G) and specific organ involvement with overall survival (OS) in 9,521 patients across 14 studies involving atezolizumab as mono (IO) or with chemo/targeted (C-IO) therapy as compared with chemo/targeted therapy (C) in advanced non-small cell lung, small-cell lung, renal cell, urothelial, and triple-negative breast cancers. We used a mixed-effect Cox proportional hazard model for time-varying covariates to address immortal-time bias; adjusted for baseline factors associated with irAEs and OS to control for confounding bias; and focused on five common irAEs (dermat
Source: jitc.bmj.comCategories: General Medicine News, Hem/OncsTweet-
Pleased to publish the largest study evaluating assoc btwn specific irAEs & IO outcomes @jitcancer: - 9521pts in 14 atezo mono/combo trials - G1-2 skin irAE, thyroid, pneumonitis assoc ⬆️OS p<0.05 - G3-4 pneu, colitis assoc ⬇️OS p<0.01 @OncoAlert #LCSM https://t.co/B5G1iOoqFF
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Mashup Score: 19
Background The association between safety and efficacy of immune checkpoint inhibitors is known, but the correlation between severity and impact of specific organ involvement by immune-related adverse events (irAE) and cancer outcomes is poorly understood. Most irAEs are mild-to-moderate but severe irAEs may pose clinical management challenges and affect patient outcomes. Methods We assessed the association between irAE grade (G) and specific organ involvement with overall survival (OS) in 9,521 patients across 14 studies involving atezolizumab as mono (IO) or with chemo/targeted (C-IO) therapy as compared with chemo/targeted therapy (C) in advanced non-small cell lung, small-cell lung, renal cell, urothelial, and triple-negative breast cancers. We used a mixed-effect Cox proportional hazard model for time-varying covariates to address immortal-time bias; adjusted for baseline factors associated with irAEs and OS to control for confounding bias; and focused on five common irAEs (dermat
Source: jitc.bmj.comCategories: General Medicine News, Oncologists1Tweet-
Proud to share our recent publication in Journal for ImmunoTherapy of Cancer, based on data from over 9,500 patients across 14 studies, showing that low-grade immune-related adverse events (#irAEs) are linked to OS https://t.co/Us5OuCfu00
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Mashup Score: 10
Background Immuno-STATs are modular fusion proteins designed for the selective activation of tumor antigen specific CD8+ T cells. CUE-102, the second Immuno-STAT in clinical trials, is composed of a human leukocyte antigen (HLA) complex, HLA-A*02:01, a peptide epitope derived from the Wilms Tumor 1 (WT1) protein, and 4 molecules of reduced affinity human interleukin-2 (IL-2), designed to bind, expand, and activate WT1-specific cytotoxic CD8+ T cells with the potential to enhance anti-tumor immunity in patients with WT1+ cancers. Here we present updated results from the dose escalation and expansion phases of the study of the CUE-102-01 study. Methods CUE-102-01 is a phase 1, 2-part study evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary antitumor activity of CUE-102 monotherapy administered every three weeks in HLA-A*02:01 positive patients with WT1+ recurrent/metastatic colorectal (CRC), gastric (GA)/gastroesophageal Jun
Source: jitc.bmj.comCategories: General Medicine News, Oncologists1Tweet-
Tomorrow at #SITC24, Dae Won Kim, PhD presents a phase 1 trial of CUE-102, a WT1-pHLA-IL2-Fc T cell engager, in HLA-A*0201+ patients with WT1-positive recurrent/metastatic cancers. #MoffittSITC24 ⏰: 11/9 9:00 a.m. CT 📍: Grand Ballroom AB Learn more ➡️ https://t.co/q7V6FHDBSM… https://t.co/NRbgPWsU0R https://t.co/bcK14n8r31
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Mashup Score: 91363 Evaluation of a novel Merkel cell carcinoma mouse model and response to anti-PD-1 immunotherapy - 14 day(s) ago
Background Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer linked to Merkel cell polyomavirus (MCPyV) or ultraviolet radiation-induced mutations in RB1 and TP53. While immunotherapy targeting the programmed cell death-1 (PD-1) pathway has shown promise, response rates in single-agent anti-PD1-based therapies are over 50%. Nevertheless, resistance to immunotherapy remains a significant challenge. The lack of targeted agents or highly effective strategies for recurrent or immunotherapy-refractory MCC further complicates the situation. Developing an appropriately credentialed immunocompetent animal model is crucial to tackle these issues. Our novel mouse model provides a platform for investigating immunotherapy resistance and developing therapeutic strategies, thus offering a significant step forward in the field. Methods and Results We undertook a unique and successful approach to developing our novel mouse model. Based on Foundation One profiles testing ove
Source: jitc.bmj.comCategories: General Medicine News, Oncologists1Tweet-
During #SITC24, Karol Prieto, PhD presents an evaluation of a novel Merkel cell carcinoma mouse model and anti-PD-1 therapy response. #MoffittSITC24 ⏰: 11/8 9 a.m. CT 📍: Grand Ballroom AB Learn more ➡️ https://t.co/0YaF9xceFI @sitcancer https://t.co/VvRAxV6tKx
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Mashup Score: 8230 Mannose supplementation: a strategy for metabolically driving a stem-like T cell program for improved tumor control - 14 day(s) ago
Background Adoptive T cell immunotherapy as a ‘living drug’ has brought cures to many previous untreatable cancers, but persistence and anti-tumor efficacy are commonly compromised by the cellular differentiation during the ex vivo expansion required to generate adequate cell numbers for therapy. Decoupling expansion from naturally linked differentiation could provide a strategy for generating T cell products with the capacity for self-renewal, persistence and enhanced efficacy. Cellular metabolic reprogramming can contribute to the preservation of T cell stemness, and interrogation of metabolic regulatory circuits governing and directing T cell fate differentiation has the potential to lead to development of effective metabolic intervention strategies for T cell immunotherapy. Methods We first identified specific metabolic pathways that anti-correlated with T cell exhaustion and are shared across contexts, by applying a novel computational framework that analyzes single-cell metabolic
Source: jitc.bmj.comCategories: General Medicine News, Oncologists1Tweet-
Fred Hutch at #SITC24: Catch @suyapeng's poster session on how a type of sugar called mannose helps #CARTcells avoid exhaustion and fight against #cancer. 🗓️ Nov. 9, 7:10 p.m.📍 Level 1 - Exhibit Halls AB 👉 https://t.co/V3yWNGmhtw https://t.co/0VXMSGzXOM
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Mashup Score: 22900 An iron-rich subset of macrophages promotes tumor growth through a Bach1-Ednrb axis - 14 day(s) ago
Background Tumor associated macrophages (TAMs) frequently comprise the most abundant leukocyte population within the tumor microenvironment (TME). TAMs are phenotypically diverse and can be polarized towards either pro- or anti-tumor functions by signals within the TME. While microvascular dysfunction with red blood cell (RBC) extravasation and intra-tumoral hemorrhage are hallmarks of solid tumors,1 the role of RBCs and heme in polarizing TAMs within the TME is not known. Methods We performed single cell RNA-seq (scRNA-seq) on multiple murine mouse models of sarcoma, including a syngeneic fibrosarcoma (FS) transplant model. Iron-rich TAMs were isolated for downstream analysis using magnetic column-based fractionation. FS flank tumors were also generated in LysMCre:Ednrbflox/flox and Bach1-/- mice. Results scRNA-seq of murine sarcomas identified a population of TAMs with significant enrichment for heme and iron metabolism pathways (figure 1). Sequencing of iTAMs isolated via magnetic c
Source: jitc.bmj.comCategories: General Medicine News, Oncologists1Tweet-
Targeting Ednrb in a unique population of iron-rich tumor associated macrophages in solid tumors represents a novel immunotherapeutic approach, our Dr. @IanFolkert shared at #SITC24. Learn more (Abstract 900): https://t.co/Z2ZPLpuPxt @SITCancer #EndCancer https://t.co/S9VoVhqIqQ
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Mashup Score: 151102 Engineering cellular backpacks to deliver therapies to ‘undruggable’ p53 in lung cancer - 14 day(s) ago
Background We have developed novel therapeutics using mechanistic insights that we have unveiled over the last several years. TP53 has long been known as an ‘undruggable’ target due to its fundamental roles in controlling key cellular functions and its role as a transcription factor. We have shown that one way to therapeutically target p53 deficient and mutant tumors is through the down regulation of ∆Np63 using genetically engineered mouse models and xenograft models that down regulation of ∆Np63 in thymic lymphomas deficient for p53, lung adenocarcinomas and squamous cell carcinomas mutant for p53, and cutaneous squamous cell carcinomas resulted in rapid tumor regression. Methods Based on these data, we developed a screen to identify compounds to inhibit ∆Np63 expression. Using this approach, we identified HDAC inhibitors and pramlintide (an FDA-approved for diabetes therapy in combination with insulin) as potent inhibitors of ∆Np63 expression and induced tumor regression. Results We
Source: jitc.bmj.comCategories: General Medicine News, Oncologists1Tweet-
At #SITC24, Elsa Flores, PhD(@LabElsaFlores) presents on engineering cellular backpacks to target "undruggable" p53 in lung cancer. #MoffittSITC24 ⏰: 11/9 9:00 a.m. CT 📍: Grand Ballroom AB Learn more ➡️ https://t.co/NXx1nm42ad @sitcancer https://t.co/OjKeDBTsdo
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Mashup Score: 141018 Leveraging innate immune sensors to generate durable anti-glioma adaptive immune responses - 14 day(s) ago
Background Glioblastoma harbors a tumor microenvironment (TME) that is mostly devoid of effector T cells but is dominated by immunosuppressive microglia, macrophages, and myeloid-derived suppresser cells. Innate immune cells in the TME have impaired phagocytosis and antigen presentation and are inadequate for triggering the immune activating signals needed for anti-tumor effector responses. Glioblastoma tumors further restrict phagocytosis and subsequent tumor antigen presentation via CD47 upregulation. We show in the Qki-/- Pten-/- P53-/- (QPP) tumor model, which reflects the immunosuppressive and immune checkpoint blockade resistant phenotypes of human glioblastoma, that agonists of the Stimulator of Interferon Genes (STING) dsDNA sensing pathway induce proinflammatory conversion of the TME and synergize with CD47 blockade to generate curative responses. Methods Using the synthetic cyclic di-nucleotide STING agonist IACS-8803 (8803; IMGS-203) and the anti-CD47 clone MIAP-410 we treat
Source: jitc.bmj.comCategories: General Medicine News, Oncologists1Tweet-
Research led by Spencer Lea, a graduate student in the @DrCurran Laboratory investigated ways to leverage innate immune sensors to generate durable anti-glioma adaptive immune responses. Learn more (Abstract 1018): https://t.co/icaPigIu4x @SITCancer #SITC24 #EndCancer https://t.co/D9hAA4KQAG
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Mashup Score: 40896 VCAM-1+ tumor associated macrophages form perivascular tumor niches and drive resistance to anti-CTLA-4 therapy - 14 day(s) ago
Background Immune checkpoint inhibitors (ICI) unleash T cell control of tumors, but are undermined by immunosuppressive myeloid cells. Tumor associated macrophages (TAM) are a heterogenous group of myeloid cells that can exert both immunostimulatory and immunosuppressive effects in the tumor microenvironment (TME). Thus, understanding the biology of TAM subsets that promote resistance or response to ICI will yield novel targets beyond the canonical phenotypical TAM markers to reverse ICI resistance. Methods Intradermal melanoma B16F10 cells and MT4 orthotopic pancreatic cancer cells were used to establish in vivo tumor models. Flow cytometry analysis was used to phenotype immune cell types in mouse tumors and ex-vivo co-cultures. FACS-sorted VCAM-1+ TAMs were used in adoptive transfer experiments and ex-vivo functional assays. VCAM-1+ TAM gene signature was derived from B16F10 and MT4 scRNAseq data of tumor-infiltrating immune cells and publicly available human melanoma scRNAseq datase
Source: jitc.bmj.comCategories: General Medicine News, Oncologists1Tweet-
How do VCAM-1 positive tumor associated macrophages affect immune checkpoint inhibitor resistance? Our Dr. Mehdi Chaib from the @JimAllisonPhD lab shared findings at #SITC24. Learn more (Abstract 896): https://t.co/1AYJmjph8S @ChaibImmune @SITCancer #EndCancer https://t.co/rmS4F2y3hr
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New #OpenAccess review from the @MDAndersonNews IOTOX team led by Mimi Wang in @jitcancer Systematic review of immune checkpoint inhibitor-related gastrointestinal, hepatobiliary, and pancreatic adverse events https://t.co/kVON4fk2Mb