A5050774369- Cancer Immunotherapy and Biomarkers
- Inflammatory mediators and NSAID effects
- Eicosanoids and Hypertension Pharmacology
- Immunotherapy and Immune Responses
- interferon and immune responses
- Synthesis of β-Lactam Compounds
- Virus-based gene therapy research
- CAR-T cell therapy research
- Radiopharmaceutical Chemistry and Applications
- Glioma Diagnosis and Treatment
- Cancer, Stress, Anesthesia, and Immune Response
- Estrogen and related hormone effects
- Nanoplatforms for cancer theranostics
- Advanced Radiotherapy Techniques
- Cancer, Hypoxia, and Metabolism
- Phagocytosis and Immune Regulation
- Chemokine receptors and signaling
- Neuroblastoma Research and Treatments
- Immune cells in cancer
- Mathematical Biology Tumor Growth
- Radiomics and Machine Learning in Medical Imaging
- Medical Imaging Techniques and Applications
- Cancer Research and Treatments
- Herpesvirus Infections and Treatments
- Complement system in diseases
Caribou Biosciences (United States)
2023-2024
Johns Hopkins Medicine
2014-2023
Johns Hopkins University
2013-2023
Tempest Technologies (United States)
2021-2023
Aduro BioTech (United States)
2018-2022
Sidney Kimmel Comprehensive Cancer Center
2017-2020
Sidney Kimmel Cancer Center
2018
Bloomberg (United States)
2018
University of Baltimore
2015
Abstract The immune-modulating effects of radiotherapy (XRT) have gained considerable interest recently, and there been multiple reports synergy between XRT immunotherapy. However, additional preclinical studies are needed to demonstrate the antigen-specific nature radiation-induced immune responses elucidate potential mechanisms with Here, we ability stereotactic induce endogenous when it is combined anti–PD-1 checkpoint blockade Using small animal radiation research platform (SARRP),...
Intratumoral (IT) STING activation results in tumor regression preclinical models, yet factors dictating the balance between innate and adaptive anti-tumor immunity are unclear. Here, clinical candidate agonist ADU-S100 (S100) is used an IT dosing regimen optimized for to uncover requirements a T cell-driven response compatible with checkpoint inhibitors (CPIs). In contrast high-dose ablative regimens that result systemic S100 distribution, low-dose immunogenic induce local of tumor-specific...
Abstract Purpose: In the proper context, radiotherapy can promote antitumor immunity. It is unknown if elective nodal irradiation (ENI), a strategy that irradiates tumor-associated draining lymph nodes (DLN), affects adaptive immune responses and combinatorial efficacy of with checkpoint blockade (ICB). Experimental Design: We developed preclinical model to compare stereotactic (Tumor RT) or without ENI examine immunologic differences between techniques spare irradiate DLN. Results: Tumor RT...
The cGAS-STING cytosolic DNA sensing pathway may play an integral role in the initiation of antitumor immune responses. Studies evaluating immunogenicity various cyclic dinucleotide (CDN) STING agonists administered by intratumoral (i.t.) injection showed potent induction inflammation, tumor necrosis, and, some cases, durable tumor-specific adaptive immunity. However, specific mechanisms underlying these responses remain incompletely defined. majority studies have focused on effect CDNs...
Abstract Purpose: Immune responses to antigens originating in the central nervous system (CNS) are generally attenuated, as collateral damage can have devastating consequences. The significance of this finding for efficacy tumor-targeted immunotherapies is largely unknown. Experimental Design: B16 murine melanoma model was used compare cytotoxic against established tumors CNS and periphery. Cytokine analysis tissues from brain tumor–bearing mice detected elevated TGFβ secretion microglia...
Immune checkpoint blockade has shown promising antitumor activity against a variety of tumor types. However, responses in castration-resistant prostate cancer remain relatively rare—potentially due to low baseline levels infiltration. Using an immunocompetent cMyc-driven model (Myc-CaP), we sought understand the immune infiltrate induced by androgen deprivation therapy (ADT) and leverage that infiltration toward therapeutic benefit. flow cytometry, qPCR IHC, quantified ADT-induced terms cell...
Glioblastoma (GBM) is a poorly immunogenic neoplasm treated with focused radiation. Immunotherapy has demonstrated synergistic survival effects stereotactic radiosurgery (SRS) in murine GBM. GITR co-stimulatory molecule expressed constitutively on regulatory T-cells and by effector upon activation. We tested the hypothesis that anti-GITR monoclonal antibody (mAb) SRS together would confer an immune-mediated benefit glioma using orthotopic GL261 model.Mice received 10 days after implantation....
Cancer immunotherapies often modulate macrophage effector function by introducing either targeting antibodies that activate Fcγ receptors (FcγRs) or blocking disrupt inhibitory SIRPα-CD47 engagement. However, how these competing signals are integrated is poorly understood, raising questions about to effectively titrate immune responses. Here, we find phagocytic decisions regulated the ratio of activating ligand over a broad range absolute molecular densities. Using both endogenous and...
While the role of prostaglandin E2 (PGE2) in promoting malignant progression is well established, how to optimally block activity PGE2 signaling remains be demonstrated. Clinical trials with pathway targeted agents have shown but without sufficient significance or dose-limiting toxicities that prevented approval. signals through four receptors (EP1–4) modulate tumor progression. EP2 and EP4 exacerbates pathology immunosuppressive potentiating cAMP production. EP1 EP3 has opposite effect...
The morphogenic process of convergent thickening (CT) was originally described as the mediolateral convergence and radial explanted ventral involuting marginal zone (IMZ)
The chemokine MIP3α (CCL20) binds to CCR6 on immature dendritic cells. Vaccines fusing gp100 have been shown be effective in therapeutically reducing melanoma tumor burden and prolonging survival a mouse model. Other studies provided evidence that interleukin-10 (IL-10) neutralizing antibodies (αIL-10) enhance immunologic therapies by modulating the tolerogenic microenvironment. In current study, we utilized B16F10 syngeneic model demonstrate for first time therapy IL-10 enhances antitumor...
TPS6586 Background: CAR-T cell therapies have shown significant clinical benefit in treating adults with many hematologic malignancies. In acute myeloid leukemia (AML), a challenge the development of has been limitation suitable target antigens since are also expressed on hematopoietic stem cells (HSCs). The antigen C-type lectin-like molecule-1 (CLL-1) emerged as an attractive therapeutic due to its expression AML mature blasts and leukemic absence HSCs. CB-012 is allogeneic therapy that...
TPS2696 Background: Prostaglandin E2 (PGE2) is a bioactive lipid that promotes cancer through diverse mechanisms including stimulating tumor proliferation, enhancing angiogenesis and suppressing immune function in the microenvironment. PGE2 produced by cells upregulation of cyclooxygenase-2 (COX-2) also key mediator adaptive resistance to checkpoint inhibitor therapy. While signaling important cancer, how best inhibit for treatment under investigation. Inhibition COX enzymes (e.g., with...
SUMMARY We characterize the morphogenic process of convergent thickening (CT), which occurs in involuting marginal zone (IMZ) during gastrulation Xenopus , African clawed frog. CT was described previously as tendency explants ventral IMZ to converge their circumblastoporal dimension and thicken radial (Keller Danilchik 1988). Here we show that from onset gastrulation, initially throughout pre-involution IMZ. suggest is driven by an increase interfacial tension between deep its epithelium,...
Abstract Genetic evidence from human disease and mouse genetic knock-out studies identify the Stimulator of Interferon Genes (STING) pathway as a critical innate immune sensor for development immunity. Tumor cells can evolve to avoid recognition through inactivating STING by diverse mechanisms, indicating that it is important generating tumor-specific However, clinical activity agonists given intratumoral (IT) administration has not compared well preclinical studies. The scientific...
Abstract Background: STING is an innate immune sensor critical for the development of immunity. Tumor cells can inactivate pathway to avoid recognition, emphasizing its importance in generating tumor-specific Broad activation advanced cancers may be required initiate CD8+ T cell priming against unique antigenic repertoires among distinct metastases and reverse immune-suppressive TME. Due ubiquitous expression, systemic delivery untargeted agonists not achieve a therapeutic index. In...
Abstract Background: We previously found upregulation of the cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) pathway in tumor microenvironment (TME) cancer types that respond poorly to anti-PD-1 therapy, and showed TME-resident cytokines such as IL-1B induce COX-2 expression human myeloid cells. To investigate a potential role for COX-2/PGE2 resistance, we studied PGE2-mediated effects on T cells their dependence prostaglandin (EP) receptor signaling. Methods: Monocytes (Monos) were enriched...
Abstract Stimulator of interferon genes (STING) is a critical component an innate immune pathway that activates robust antiviral and antitumor responses in mouse models. Activation the STING by intratumoral (IT) injection synthetic cyclic dinucleotides (CDNs) being explored as cancer therapy has shown potent activity preclinical Here we assessed benefit combining checkpoint blockade with ADU-S100 (MIW815), CDN under clinical evaluation, different syngeneic tumor In mice bearing dual flank...
Meeting abstracts One of the current questions surrounding CD4 T regulatory cells (Tregs) is role natural and induced Tregs in tumor tolerance. Natural are that leave thymus expressing FoxP3 displaying potential. Induced as a naïve