A5057529077- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Galectins and Cancer Biology
- T-cell and B-cell Immunology
- Immune cells in cancer
- Immune Response and Inflammation
- Asthma and respiratory diseases
- Cancer Mechanisms and Therapy
- Inflammation biomarkers and pathways
- Antimicrobial Peptides and Activities
- Sepsis Diagnosis and Treatment
- Pediatric health and respiratory diseases
- Neonatal Respiratory Health Research
- Prostate Cancer Treatment and Research
- Brain Metastases and Treatment
- Lung Cancer Treatments and Mutations
- Research on Leishmaniasis Studies
- Cancer, Stress, Anesthesia, and Immune Response
- Multiple Sclerosis Research Studies
- Mast cells and histamine
- Sphingolipid Metabolism and Signaling
- Glycosylation and Glycoproteins Research
- Diverticular Disease and Complications
Providence Portland Medical Center
2013-2023
Cancer Research Center
2013-2023
Oregon Health & Science University
2009-2020
Providence Health & Services
2013-2019
Data Harbor (United States)
2015
Oregon Medical Research Center
2014
Ligation of the TNF receptor family costimulatory molecule OX40 (CD134) with an agonist anti-OX40 monoclonal antibody (mAb) enhances antitumor immunity by augmenting T-cell differentiation as well turning off suppressive activity FoxP3(+)CD4(+) regulatory T cells (Treg). In addition, antibody-mediated blockade checkpoint inhibitor CTLA-4 releases "brakes" on to augment tumor immunotherapy. However, monotherapy these agents has limited therapeutic benefit particularly against poorly...
Significance Several immunotherapies are approved for treating cancer patients, including aCTLA-4 (anti–cytotoxic T-lymphocyte–associated protein 4; ipilimumab) and anti–PD-1 (anti-programmed cell death 1; nivolumab; pembrolizumab), but the best clinical results coming from combination immunotherapy. Our research demonstrates that aOX40 (anti-CD134)/aCTLA-4 immunotherapy can lead to a potentially tumor-promoting Th2-cytokine milieu (IL-4, IL-5, IL-13) when relying on endogenous antigen...
Eosinophils are best known as the predominant cellular infiltrate associated with asthma and parasitic infections. Recently, numerous studies have documented presence of Toll-like receptors (TLRs) on surfaces eosinophils, suggesting that these leukocytes may participate in recognition killing viruses bacteria. However, significance this role innate immune response to bacterial infection is largely unknown. Here we report a novel for eosinophils antibacterial defenders host response. Isolated...
The immune response in sepsis is characterized by overt dysfunction. Studies indicate immunostimulation represents a viable therapy for patients. One study suggests potentially protective role interleukin 5 (IL-5) sepsis; however, the loss of eosinophils this disease presents paradox.To assess and eosinophil-independent effects IL-5 sepsis.We assessed administration on survival, bacterial burden, cytokine production after polymicrobial sepsis. In addition, we examined macrophage phagocytosis...
Treatment with an agonist anti-OX40 antibody (aOX40) boosts anti-tumor immunity by providing costimulation and driving effector T cell responses. However, tumor-induced immune suppression contributes significantly to poor response rates aOX40 therapy, thus combining other agents that relieve tumor-mediated may improve outcomes. Once such target is galectin-3 (Gal-3), which drives immunosuppression increasing macrophage infiltration M2 polarization, restricting TCR signaling, inducing...
Breast cancer brain metastases (BCBM) are a common and devastating complication of metastatic breast with conventional systemic therapies demonstrating limited effectiveness. Consequently, radiotherapy (RT) ± surgery remains the cornerstone BCBM management. Because preclinical clinical evidence indicate that immune checkpoint blockade (ICB) may synergize RT to promote tumor regression, we explored safety efficacy concurrent tremelimumab-mediated cytotoxic T-lymphocyte associated protein 4...
Immune checkpoint inhibitors are transforming the way cancer is treated. However, these therapies do not benefit all patients and frequently cause significant immune-related adverse events. Biomarkers that identify with a favorable early response to therapy essential for guiding treatment decisions improving patient outcomes. In this report of our study, we present evidence shortly after administration dual PD-1/CTLA-4 blockade, proinflammatory capacity peripheral lymphocytes predictive...
It is becoming clear that combination strategies will be necessary to augment cancer immunotherapy. We report anti-OX40/anti-CTLA-4 mAb immunotherapy improves survival by enhancing effector T cell expansion and function, even while inducing Th2 cytokine production. Furthermore, IL-4 blockade in addition therapy significantly improved anti-tumor efficacy.
Meeting abstracts Immunosuppression and reduced cytolytic function of tumor-infiltrating lymphocytes are major obstacles to creating effective therapies for patients. It is known that Galectin-3 (Gal3), a lectin family member, expressed secreted by numerous cancers immune cell subsets.
Several members of the common gamma chain (gc) cytokine family are already approved (IL-2) or actively being developed as vaccine adjuvants and cancer immunotherapies. Studies have indicated that co-administration gc cytokines may enhance efficacy immunotherapies function via direct activation co-stimulatory T cell receptors. To define specific influence on capacity CD8(+) cells identify combinations with synergistic potential, we investigated impact differentiation transcriptional profile...
Mounting an immune response sufficient to eradicate a tumor is the goal of modern immunotherapy. Single agent therapies with checkpoint inhibitors or costimulatory molecule agonists are effective only for small portion all treated patients. Combined therapy, e.g., CTLA-4 and PD-1 blockade, more treatment modality, but in preclinical studies OX40 agonism blockade using monoclonal antibodies (aOX40/aCTLA-4) failed induce regression larger, established tumors. We hypothesized that...
Numerous preclinical studies have demonstrated that combination immunotherapy can significantly reduce tumor growth and improve overall survival as compared to monotherapy. Furthermore, dual CTLA-4/PD-1 checkpoint blockade recently received FDA-approval for patients with metastatic melanoma, becoming the first garner this designation in a rapidly evolving field. Despite progress, majority of do not respond treatment, underscoring critical need more effective therapies. We been investigating...
Abstract Immunosuppression and reduced cytotoxic function of tumor-infiltrating lymphocytes (TIL) are major obstacles to creating effective therapies for patients. It is known that Galectin-3 (Gal3), a lectin family member, expressed secreted by numerous cancers immune cell subsets. Serum Gal3 expression higher in patients with metastatic versus non-metastatic disease, associated survival melanoma. Furthermore, has been implicated disease progression via the promotion angiogenesis...
Meeting abstracts Ligation of the TNF receptor family co-stimulatory molecule OX40 (CD134) with an agonist anti-OX40 mAb enhances anti-tumor immunity by augmenting T cell differentiation as well turning off suppressive activity FoxP3+CD4+ regulatory cells (Treg). In addition, antibody-
Meeting abstracts Immunotherapy is gathering momentum as a primary therapy for cancer patients. However, monotherapies have limited efficacy in improving outcomes and only benefit subset of Combination therapies targeting multiple pathways can augment an immune response to further
Several members of the common gamma chain (gc) cytokine family are already approved (IL-2) or actively being developed as vaccine adjuvants and cancer immunotherapies. Studies have indicated that co-administration gc cytokines may enhance efficacy immunotherapies function via direct activation co-stimulatory T cell receptors. To define specific influence on capacity CD8+ cells identify combinations with synergistic potential, we investigated impact differentiation transcriptional profile...
Meeting abstracts Targeted immunotherapy, such as anti-CTLA-4 and anti-PD-1, has proven effective in treating cancer patients. However, despite these advances, remains the second leading cause of death US. More strategies designed to maximize anti-tumor CD8 T cell responses
Abstract Ligation of the TNF receptor family co-stimulatory molecule OX40 (CD134) with an agonist anti-OX40 mAb enhances anti-tumor immunity by augmenting CD4 and CD8 T cell clonal expansion, effector differentiation, as well turning off suppressive activity FoxP3+CD4+ regulatory cells (Treg). Moreover, targeted blockade checkpoint inhibitor CTLA-4 on Treg boosting responses alleviating capacity Treg. However, monotherapy or anti-CTLA-4 can have limited efficacy, particularly against poorly...
<div>Abstract<p>Ligation of the TNF receptor family costimulatory molecule OX40 (CD134) with an agonist anti-OX40 monoclonal antibody (mAb) enhances antitumor immunity by augmenting T-cell differentiation as well turning off suppressive activity FoxP3<sup>+</sup>CD4<sup>+</sup> regulatory T cells (Treg). In addition, antibody-mediated blockade checkpoint inhibitor CTLA-4 releases “brakes” on to augment tumor immunotherapy. However, monotherapy these agents...
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