A5054552399- Cancer Immunotherapy and Biomarkers
- Bone health and treatments
- Immunotherapy and Immune Responses
- Radiopharmaceutical Chemistry and Applications
- Bone Metabolism and Diseases
- Immune Cell Function and Interaction
- Nanoplatforms for cancer theranostics
- CAR-T cell therapy research
- interferon and immune responses
- Boron Compounds in Chemistry
- Inflammatory mediators and NSAID effects
- Chemokine receptors and signaling
- TGF-β signaling in diseases
- Brain Metastases and Treatment
- Cancer, Hypoxia, and Metabolism
- NF-κB Signaling Pathways
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer Research and Treatments
- Boron and Carbon Nanomaterials Research
- Medical Imaging Techniques and Applications
- Lung Cancer Research Studies
- Estrogen and related hormone effects
- Cancer-related molecular mechanisms research
- Neonatal Respiratory Health Research
- Inhalation and Respiratory Drug Delivery
University of Wisconsin–Madison
2019-2025
Seoul National University Dental Hospital
2016-2018
Seoul National University
2012-2017
Korea Institute of Oriental Medicine
2012
Seoul Veterans Hospital
1997
Low-dose targeted radionuclide therapy combined with immune checkpoint inhibition enhances complete response rates in preclinical tumor models.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by uncontrolled joint inflammation and destruction of bone cartilage. We previously reported that C-X-C motif chemokine 10 (CXCL10; also called IP-10) has important roles in arthritis. However, the specific mechanisms which CXCL10 regulates recruitment inflammatory cells production osteoclastogenic cytokines RA progression are not fully understood. Bone marrow-derived macrophages CD4+ T were isolated from wild-type (WT),...
Abstract Radiation therapy (RT) activates an in situ vaccine effect when combined with immune checkpoint blockade (ICB), yet this may be limited because RT does not fully optimize tumor antigen presentation or overcome suppressive mechanisms the tumor-immune microenvironment. To this, we develop a multifunctional nanoparticle composed of polylysine, iron oxide, and CpG (PIC) to increase presentation, ratio M1:M2 tumor-associated macrophages, enhance stimulation type I interferon response...
Radiation therapy (RT) activates multiple immunologic effects in the tumor microenvironment (TME), with diverse dose-response relationships observed. We hypothesized that, contrast homogeneous RT, a heterogeneous RT dose would simultaneously optimize activation of immunogenic single TME, resulting more effective antitumor immune response. Using high-dose-rate brachytherapy, we treated mice bearing syngeneic tumors fraction at ranging from 2 to 30 gray. When combined dual checkpoint...
Amplification of the chemokines CXCL10 and RANKL has been suggested to promote osteoclast differentiation osteolytic bone metastasis, but a function for endogenous in these processes is not well established. In this study, we show that critical recruit cancer cells bone, support formation metastases. Neutralizing antibody reduced migration expressing receptor CXCR3, loss CXCR3 or decreased tumor burden vivo. Bone colonization augmented host production CXCL10, which was required growth...
Clinical interest in combining targeted radionuclide therapies (TRT) with immunotherapies is growing. External beam radiation therapy (EBRT) activates a type 1 interferon (IFN1) response mediated via stimulator of genes (STING), and this critical to its therapeutic interaction immune checkpoint blockade. However, little known about the time course IFN1 activation after EBRT or whether may be induced by decay TRT source.
Background Radiation therapy (RT) elicits DNA double-strand breaks, resulting in tumor cytotoxicity and a type I interferon (IFN) response via stimulator of genes (STING) activation. We investigated whether combining RT with an ataxia-telangiectasia mutated inhibitor promoted these effects amplified immunity. Methods Mice-bearing syngeneic flank tumors (MOC2 head neck squamous cell carcinoma or B78 melanoma) were treated tumor-directed oral administration AZD0156. Specific immune depletion,...
Abstract Purpose/Objective: Radiopharmaceutical therapy (RPT) enables the systemic delivery of an inherently heterogeneous dose radiation. The RPT heterogeneity is created by a tumor’s non-uniform perfusion and variation in target expression. Radiation known to immunomodulate tumor microenvironment (TME) dose-dependent manner. hypothesis that with distribution, delivering low high gradient single TME, will activate multiple dependent immune effects are more effective promoting priming...
The chemokine CXCL10 and its receptor CXCR3 play a role in breast cancer metastasis to bone osteoclast activation. However, the mechanism of CXCL10/CXCR3-induced intracellular signaling has not been fully investigated. To evaluate CXCL10-induced cellular events mouse cell line 4T1, we developed new synthetic antagonist JN-2. In this study, observed that secretion supernatant 4T1 cells was gradually increased during growth. JN-2 inhibited basal expression motility cells. Treatment with P65,...
Background Current clinical trials are using radiation therapy (RT) to enhance an antitumor response elicited by high-dose interleukin (IL)-2 or immune checkpoint blockade (ICB). Bempegaldesleukin (BEMPEG) is investigational CD122-preferential IL-2 pathway agonist with prolonged in vivo half-life and preferential intratumoral expansion of T effector cells over regulatory cells. BEMPEG has shown encouraging safety efficacy when used combination PD-1 blockade. In this study, we investigated...
Abstract Background Most patients with estrogen receptor positive (ER+) breast cancer do not respond to immune checkpoint inhibition (ICI); the tumor microenvironment (TME) of these cancers is generally immunosuppressive and contains few tumor-infiltrating lymphocytes. Radiation therapy (RT) can increase inflammation infiltration by lymphocytes but does improve responses ICIs in patients. This may result, part, from additional effects RT that suppress anti-tumor immunity, including increased...
In head and neck squamous cell carcinoma (HNSCC) tumors that over-expresses huEGFR, the anti-EGFR antibody, cetuximab, antagonizes tumor viability sensitizes to radiation therapy. However, immunologic interactions between cetuximab therapy are not well understood. We transduced two syngeneic murine HNSCC lines express human EGFR (MOC1- MOC2-huEGFR) in order facilitate evaluation of cetuximab. Cetuximab was capable inducing antibody-dependent cellular cytotoxicity (ADCC) MOC1- MOC2-huEGFR...
Background Radiation therapy (RT) has been demonstrated to generate an in situ vaccination (ISV) effect murine models and patients with cancer; however, this not routinely translated into enhanced clinical response immune checkpoint inhibition (ICI). We investigated whether the commonly used vaccine adjuvant, monophosphoryl lipid A (MPL) could augment ISV regimen consisting of combination RT ICI. Materials/methods syngeneic melanoma (B78) prostate cancer (Myc-CaP). Tumor-bearing mice...
We report an in situ vaccination, adaptable to nearly any type of cancer, that combines radiotherapy targeting one tumor and intratumoral injection this site with tumor-specific antibody interleukin-2 (IL-2; 3xTx). In a phase I clinical trial, administration 3xTx (with immunocytokine fusion IL-2, hu14.18-IL2) subjects metastatic melanoma increases peripheral CD8+ T cell effector polyfunctionality. This suggests the potential for promote antitumor immunity against tumors. poorly immunogenic...
In a syngeneic murine melanoma (MEL) model, we recently reported an in situ vaccination response to combined radiation (RT) and intra-tumoral (IT) injection of anti-GD2 hu14.18-IL2 immunocytokine (IC). This treatment resulted 71% complete durable regression 5-week tumors, tumor-specific memory T cell response, augmented systemic anti-CTLA-4 antibody checkpoint blockade. While the ability diversify anti-tumor has been reported, hypothesize that mice rendered disease-free (DF) by RT-based ISV...
Haptoglobin (Hp), a type of acute-phase protein, is known to have systemic anti-inflammatory function and modulate inflammation by directly affecting immune cells, such as T dendritic macrophages. However, the effects Hp on osteoclast differentiation are not well studied, even though precursor cells belong macrophage-monocyte lineage. In this study, we found that bone volume was reduced, number osteoclasts increased in Hp-deficient mice compared with wild-type mice. Moreover, our vitro...
Abstract Radiopharmaceutical therapies (RPT) activate a type I interferon (IFN1) response in tumor cells. We hypothesized that the timing and amplitude of this varies by isotope. compared equal doses delivered 90 Y, 177 Lu, 225 Ac vitro as unbound radionuclides vivo when chelated to NM600, tumor-selective alkylphosphocholine. Response murine MOC2 head neck carcinoma B78 melanoma was evaluated qPCR flow cytometry. Therapeutic Ac-NM600+anti-CTLA4+anti-PD-L1 immune checkpoint inhibition (ICI)...
Brain metastases develop in over 60% of advanced melanoma patients and negatively impact quality life prognosis. In a murine model, we previously showed that an situ vaccination (ISV) regimen, combining radiation treatment intratumoral (IT) injection immunocytokine (IC: anti-GD2 antibody fused to IL2), along with the immune checkpoint inhibitor anti-CTLA-4, robustly eliminates peripheral flank tumors but only has modest effects on co-occurring intracranial tumors. this study, investigated...
Osteoclasts are bone-resorbing multinucleated cells derived from the monocyte/macrophage lineage during normal and pathological bone turnover. Recently, several studies revealed that alpha-tocopheryl succinate (αTP-suc) have demonstrated potent anti-cancer activities in vitro vivo. However, effects of αTP-suc on osteoclast formation resorption remain unknown. Thus, this study, we examined differentiation resorbing activity inflammatory loss model.Osteoclast assay was performed by cocultures...