A5068558823- Immunotherapy and Immune Responses
- Immune cells in cancer
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Cancer Genomics and Diagnostics
- Chemokine receptors and signaling
- Lung Cancer Treatments and Mutations
- T-cell and B-cell Immunology
- Radiomics and Machine Learning in Medical Imaging
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Research Studies
- Colorectal Cancer Treatments and Studies
- Cell Adhesion Molecules Research
- Peptidase Inhibition and Analysis
- Epigenetics and DNA Methylation
- Inflammation biomarkers and pathways
- Cancer Research and Treatments
- Ocular Oncology and Treatments
- Immune responses and vaccinations
- RNA modifications and cancer
- Phagocytosis and Immune Regulation
- CAR-T cell therapy research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- vaccines and immunoinformatics approaches
Kaiser Permanente South San Francisco Medical Center
2022
Apexigen (United States)
2019-2021
Helix Biomedix (United States)
2021
OncoMed (United States)
2015-2018
University of California, Los Angeles
2011-2017
VA Greater Los Angeles Healthcare System
2011-2015
Gene Therapy Laboratory
2012-2015
Stanford University
2014-2015
Stanford Medicine
2015
UCLA Jonsson Comprehensive Cancer Center
2011-2013
Myeloid-derived suppressor cells (MDSC) are present in most cancer patients and potent inhibitors of T-cell-mediated antitumor immunity. Their inhibitory activity is attributed to production arginase, reactive oxygen species, inducible nitric oxide synthase, interleukin-10. Here we show that MDSCs also block T-cell activation by sequestering cystine limiting the availability cysteine. Cysteine an essential amino acid for because T lack cystathionase, which converts methionine cysteine, they...
IMpower010 (NCT02486718) demonstrated significantly improved disease-free survival (DFS) with adjuvant atezolizumab versus best supportive care (BSC) following platinum-based chemotherapy in the programmed death-ligand 1 (PD-L1)-positive and all stage II-IIIA non-small-cell lung cancer (NSCLC) populations, at DFS interim analysis. Results of first analysis overall (OS) are reported here.The design, participants, primary-endpoint outcomes have been for this phase III, open-label, : randomised...
Myeloid derived suppressor cells (MDSC) are important regulators of immune responses. We evaluated the mechanistic role MDSC depletion on antigen presenting cell (APC), NK, T activities and therapeutic vaccination responses in murine models lung cancer.
Abstract Purpose: Chemoimmunotherapy (chemoIO) is a prevalent first-line treatment for advanced driver-negative non–small cell lung cancer (NSCLC), with maintenance therapy given after induction. However, there significant clinical variability in the duration, dosing, and timing of induction chemoIO. We used circulating tumor DNA (ctDNA) monitoring to inform outcomes patients NSCLC receiving Experimental Design: This retrospective study included 221 from phase III trial...
LBA8035 Background: IMpower010 (NCT02486718) met its primary endpoint of significant DFS improvement with atezo vs BSC after adj chemotherapy in resected NSCLC the PD-L1 TC ≥1% and all-randomized stage II-IIIA populations, leading to worldwide approval for or ≥50% NSCLC. At OS IA1, a trend favoring was seen population. Here we report findings from FA IA2. Methods: The study design has been previously described (Felip et al, Lancet 2021). secondary endpoints were tested hierarchically:...
Background Based on our preclinical findings, we are assessing the efficacy of intratumoral injection dendritic cells (DC) transduced with an adenoviral vector expressing secondary lymphoid chemokine (CCL21) gene (Ad-CCL21-DC) in a phase I trial advanced non-small cell lung cancer (NSCLC). While this approach shows immune enhancement, preparation autologous DC for CCL21 genetic modification is cumbersome, expensive and time consuming. We evaluating non-DC based which utilizes vault...
Abstract Background Chronic neuroinflammation is an important component of Alzheimer’s disease and could contribute to neuronal dysfunction, injury loss that lead progression. Multiple clinical studies implicate tumor necrosis factor-α as inflammatory mediator neurodegeneration in patients with because elevated levels this cytokine the cerebrospinal fluid, hippocampus cortex. Current interventions are symptomatic treatments limited efficacy do not address etiology. Thus, a critical need...
Programmed death ligand 1 (PDL1, or B7-H1) is expressed constitutively induced by IFN-γ on the cell surface of most human cancer cells and acts as a "molecular shield" protecting tumor from T cell-mediated destruction. Using seven lines representing four histologically distinct solid tumors (lung adenocarcinoma, mammary carcinoma, cutaneous melanoma, uveal melanoma), we demonstrate that transfection with gene encoding costimulatory molecule CD80 prevents PDL1-mediated immune suppression...
Abstract Tumor cells counteract innate and adaptive antitumor immune responses by recruiting regulatory T (Treg) myeloid-derived suppressor (MDSC), which facilitate escape metastatic dissemination. Here we report a role in these recruitment processes for CD81, member of the tetraspanin family proteins that have been implicated previously cancer progression. We found genetic deficiency CD81 reduced tumor growth metastasis two mouse backgrounds multiple models. Mechanistic investigations...
Abstract Background Interleukin-27 signaling is mediated by the JAK-STAT pathway via activation of STAT1 and STAT3, which have tumor suppressive oncogenic activities, respectively. Epithelial–mesenchymal transition (EMT) angiogenesis are key processes in carcinogenesis. Although IL-27 has been shown to potent anti-tumor activity various cancer models, role EMT poorly understood. In this study, we investigated regulating through modulation STAT pathways human non-small cell lung carcinoma...
Abstract Purpose: We evaluated the utility of chimeric γc homeostatic cytokine, IL-7/IL-7Rα-Fc, to restore host APC (antigen presenting cell) and T cell activities in lung cancer. Experimental Design: Utilizing murine cancer models we determined antitumor efficacy IL-7/IL-7Rα-Fc. APC, cell, cytokine analyses, neutralization CXCL9, CXCL10, IFNγ were carried out evaluate mechanistic differences activity IL-7/IL-7Rα-Fc comparison controls. Results: administration inhibited tumor growth...
Background Modifications of adjuvants that induce cell-mediated over antibody-mediated immunity is desired for development vaccines. Nanocapsules have been found to be viable and are amenable engineering immune responses. We previously showed natural nanocapsules called vaults can genetically engineered elicit Th1 protection from a mucosal bacterial infection. The purpose our study was characterize produced in response OVA within vault nanoparticles compare it another nanocarrier....
Background Tumor samples from the phase III IMpower010 study were used to compare two programmed death-ligand 1 (PD-L1) immunohistochemistry assays (VENTANA SP263 and Dako 22C3) for identification of PD-L1 patient subgroups (negative, positive, low, high expression) their predictive value adjuvant atezolizumab compared with best supportive care (BSC) in resectable early-stage non-small cell lung cancer (NSCLC). Methods expression was assessed by assay, which measured percentage tumor cells...
Abstract Uveal melanoma, the most common malignancy of eye, has a 50% rate liver metastases among patients with large primary tumors. Several therapies prolong survival metastatic patients; however, none are curative and no survive. Therefore, we exploring immunotherapy as an alternative or adjunctive treatment. melanoma may be particularly appropriate for because tumors arise in immune-privileged site express antigens to which host is not tolerized. We developing MHC class II (MHC...
Background: Myeloid derived suppressor cells (MDSC) are important regulators of immune responses.We evaluated the mechanistic role MDSC depletion on antigen presenting cell (APC), NK, T activities and therapeutic vaccination responses in murine models lung cancer.Principal Findings: Individual antibody mediated (anti-Gr1 or anti-Ly6G) enhanced antitumor activity against cancer.In comparison to controls, APC increased frequency NK effectors tumor.Compared anti-Gr1 anti-Ly6G treatment led...
An immune tolerant tumor microenvironment promotes evasion of lung cancer. Agents that antagonize tolerance will thus aid the fight against this devastating disease. Members necrosis factor receptor (TNFR) family modulate magnitude, duration and phenotype responsiveness to antigens. Among these, GITR expressed on cells functions as a key regulator in inflammatory responses. Here, we evaluate agonistic antibody (DTA-1) mono-therapy combination with therapeutic vaccination murine cancer...
Cancer cells can escape the antitumor immune response by recruiting suppressor cells. However, although innate myeloid-derived (MDSCs) and T regulatory (Treg) accumulate normally in tumor-bearing CD81-deficient mice, both populations are impaired their ability to suppress response.
Myeloid-derived suppressor cells (MDSCs) are important regulators of immune responses. These suppress the cytotoxic activities natural killer (NK)-cell and T-cell effectors promote tumor growth. We demonstrated that depleting MDSCs improve therapeutic responses to vaccination in a murine model lung cancer. This approach may prove beneficial against tumors which MDSC exert prominent immunosuppressive effects.