A5021541871- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Single-cell and spatial transcriptomics
- Immunodeficiency and Autoimmune Disorders
- Colorectal Cancer Treatments and Studies
- Cancer, Stress, Anesthesia, and Immune Response
- Nanoplatforms for cancer theranostics
- Radiopharmaceutical Chemistry and Applications
- Influenza Virus Research Studies
- Cell Image Analysis Techniques
- IL-33, ST2, and ILC Pathways
- Melanoma and MAPK Pathways
- Monoclonal and Polyclonal Antibodies Research
- Renal and related cancers
- Bioinformatics and Genomic Networks
- Brain Metastases and Treatment
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Receptor Mechanisms and Signaling
- Cancer Research and Treatments
- Immune Response and Inflammation
The University of Texas MD Anderson Cancer Center
2017-2024
Melanoma Institute Australia
2022
Baylor University
2010-2021
Baylor University Medical Center
2011
Baylor Institute for Rehabilitation
2010
A T cell subset that emerges in blood after seasonal influenza vaccinations correlates with the development of protective antibody responses.
Abstract NKTR-214 (bempegaldesleukin) is a novel IL2 pathway agonist, designed to provide sustained signaling through heterodimeric receptor βγ drive increased proliferation and activation of CD8+ T natural killer cells without unwanted expansion regulatory (Treg) in the tumor microenvironment. In this first-in-human multicenter phase I study, administered as an outpatient regimen was well tolerated showed clinical activity including shrinkage durable disease stabilization heavily pretreated...
This single-arm, phase I dose-escalation trial (NCT02983045) evaluated bempegaldesleukin (NKTR-214/BEMPEG), a CD122-preferential IL2 pathway agonist, plus nivolumab in 38 patients with selected immunotherapy-naïve advanced solid tumors (melanoma, renal cell carcinoma, and non-small lung cancer). Three dose-limiting toxicities were reported 2 of 17 during dose escalation [hypotension (n = 1), hyperglycemia metabolic acidosis 1)]. The most common treatment-related adverse events (TRAE)...
Abstract High dose interleukin-2 (IL-2) is active against metastatic melanoma and renal cell carcinoma, but treatment-associated toxicity expansion of suppressive regulatory T cells (Tregs) limit its use in patients with cancer. Bempegaldesleukin (NKTR-214) an engineered IL-2 cytokine prodrug that provides sustained activation the pathway a bias to receptor CD122 (IL-2Rβ). Here we assess therapeutic impact mechanism action NKTR-214 combination anti-PD-1 anti-CTLA-4 checkpoint blockade...
Abstract The immune mechanism leading to the generation of protective antibody responses following influenza trivalent inactivated vaccine (TIV) vaccinations remains largely uncharacterized. We recently reported that TIV vaccination induced a transient increase circulating ICOS + PD-1 CXCR3 T follicular helper (cTfh) cells in blood, which positively correlated with induction measured at day 28. However, whether and how these directly contribute response unclear. In this study, we analyzed...
T follicular helper (Tfh) cells represent a Th subset engaged in the help of B-cell responses germinal centers (GCs). Tfh abundantly express transcription repressor lymphoma 6 (Bcl6), factor that is necessary and sufficient for their development vivo. Whether or Tfh-committed are involved B outside GCs remains unclear, particularly humans. In this study, we identified previously undefined BCL6 -expressing CD4 + T-cell human tonsils. This expressed IL-7 receptor chemokine 5 (CXCR5) inducible...
Abstract Many patients with advanced melanoma are resistant to immune checkpoint inhibition. In the ILLUMINATE-204 phase I/II trial, we assessed intratumoral tilsotolimod, an investigational Toll-like receptor 9 agonist, systemic ipilimumab in anti–PD-1– melanoma. all patients, 48.4% experienced grade 3/4 treatment-emergent adverse events. The overall response rate at recommended II dose of 8 mg was 22.4%, and additional 49% had stable disease. Responses noninjected lesions expected be...
The inability of CD8+ effector T cells (Teffs) to reach tumor is an important aspect resistance cancer immunotherapy. recruitment these the microenvironment (TME) regulated by integrins, a family adhesion molecules that are expressed on cells. Here, we show 7HP349, small-molecule activator lymphocyte function-associated antigen-1 (LFA-1) and very late activation antigen-4 (VLA-4) integrin cell-adhesion receptors, facilitated preferential localization tumor-specific improved antitumor...
9553 Background: Combination immune-checkpoint inhibitors (ICIs) improved outcomes in a plethora of cancer subtypes. However, up to 60% patients (pts) receiving ipilimumab (ipi) plus nivolumab (nivo) experience grade 3/4 (G 3/4) immune-related adverse events (irAEs), often leading treatment discontinuation. We evaluated two therapeutic strategies targeting interleukin-6 receptor (IL-6R) reduce irAEs while enhancing ICls efficacy. Methods: Phase Il trial (NCT04940299) investigating...
IL-12 is important for the differentiation of T follicular helper (Tfh) cells, as well Th1 cells in humans. Still, how signals regulate Tfh versus cell remains poorly characterized. Here we aimed to determine molecular mechanisms that and function IL-12-stimulated human naive CD4(+) cells. We found T-bet promoted expression CXCR5 provide evidence does not strongly inhibit program per se but diminishes functions help B This study also suggests IRF4 plays an role driving early toward away from...
Transcription factor Tox2 plays a key role to maintain T FH phenotype and generate memory cells in both mice humans.
The Cancer Immune Monitoring and Analysis Centers - Immunologic Data Commons (CIMAC-CIDC) Network is supported by the NCI to identify biomarkers of response cancer immunotherapies across clinical trials using state-of-the-art assays. A primary platform for CIMAC-CIDC studies cytometry time flight (CyTOF), performed at all CIMAC laboratories. To ensure ability generate comparable CyTOF data labs, a multistep cross-site harmonization effort was undertaken.
TPS9600 Background: Immune checkpoint inhibitors (ICIs) are approved for multiple malignancies, however, durable remission rates with ICI monotherapy remains low. Combined treatment anti-CTLA-4 and anti-PD1 has shown higher response in several cancers but is associated up to 60% grade 3/4 immune-related adverse events (irAEs) leading frequent discontinuation. The need corticosteroids control irAEs may further diminish anti-tumor activity. A multi-disciplinary approach using clinical,...
Abstract The use of immune-checkpoint inhibitors (CPI) has become an important modality in the treatment metastatic melanoma (MM). However, most patients (pts) do not experience durable responses and new options are needed to improve clinical outcomes. Our pre-clinical studies have demonstrated that intratumoral CD40 activation synergizes with anti-PD-1 based therapy induces systemic distant anti-tumor effects. In this ongoing phase I/II study, we assessed sotigalimab (APX005M), a agonist...