A5066035608- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Phagocytosis and Immune Regulation
- Immune cells in cancer
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- T-cell and Retrovirus Studies
- Nuclear Receptors and Signaling
- Protein Degradation and Inhibitors
- Cytomegalovirus and herpesvirus research
- Viral Infectious Diseases and Gene Expression in Insects
- Glioma Diagnosis and Treatment
- Viral-associated cancers and disorders
- Galectins and Cancer Biology
- RNA Interference and Gene Delivery
- Parvovirus B19 Infection Studies
- Virus-based gene therapy research
- Lymphoma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
- Chronic Lymphocytic Leukemia Research
- Autophagy in Disease and Therapy
- Lipid metabolism and disorders
Sanofi (United States)
2021-2025
AVEO Oncology (United States)
2024
Children's Cancer Center
2007-2023
Sanofi (France)
2023
Data Harbor (United States)
2015
Dana-Farber Cancer Institute
2014
Texas Children's Hospital
2008-2013
Baylor College of Medicine
1991-2013
Houston Methodist
2008-2013
Methodist Hospital
2008-2013
Targeted T cells are emerging as effective non-toxic therapies for cancer. Multiple elements, however, contribute to the overall pathogenesis of cancer through both distinct and redundant mechanisms. Hence, targeting multiple cancer-specific markers simultaneously could result in better therapeutic efficacy. We created a functional chimeric antigen receptor-the TanCAR, novel artificial molecule that mediates bispecific activation cells. demonstrate feasibility cumulative integration...
Abstract Purpose: Glioblastoma multiforme (GBM) is the most aggressive human primary brain tumor and currently incurable. Immunotherapies have potential to target GBM stem cells, which are resistant conventional therapies. Human epidermal growth factor receptor 2 (HER2) a validated immunotherapy target, we determined if HER2-specific T cells can be generated from patients that will autologous HER2-positive GBMs their CD133-positive cell compartment. Experimental Design: 10 consecutive were...
Cancer-associated fibroblasts (CAFs), the principle component of tumor-associated stroma, form a highly protumorigenic and immunosuppressive microenvironment that mediates therapeutic resistance. Co-targeting CAFs in addition to cancer cells may therefore augment antitumor response. Fibroblast activation protein-α (FAP), type 2 dipeptidyl peptidase, is expressed on majority solid tumors making it an attractive immunotherapeutic target. To target FAP-positive we genetically modified T express...
Outcomes for patients with glioblastoma (GBM) remain poor despite aggressive multimodal therapy. Immunotherapy genetically modified T cells expressing chimeric antigen receptors (CARs) targeting interleukin (IL)-13Rα2, epidermal growth factor receptor variant III (EGFRvIII), or human 2 (HER2) has shown promise the treatment of gliomas in preclinical models and a clinical study (IL-13Rα2). However, IL-13Rα2 EGFRvIII is associated development loss variants, there are safety concerns HER2....
Glioblastoma (GBM) is the most common primary brain cancer in adults and virtually incurable. Recent studies have shown that cytomegalovirus (CMV) present majority of GBMs. To evaluate whether CMV antigens pp65 IE1, which are expressed GBMs, could be targeted by CMV-specific T cells, we measured frequency cells targeting IE1 peripheral blood a cohort 11 sequentially diagnosed CMV-seropositive GBM patients, evaluated it was feasible to expand autologous for future clinical studies. All...
The presence of T regulatory (Treg) cells in the tumor microenvironment is associated with poor prognosis and resistance to therapies aimed at reactivating anti-tumor immune responses. Therefore, depletion tumor-infiltrating Tregs a potential approach overcome immunotherapy. However, identifying Treg-specific targets drive such selective challenging. CCR8 has recently emerged as one these targets. Here, we describe GS-1811, novel therapeutic monoclonal antibody that specifically binds human...
Tumor-associated macrophages (TAM) play an important role in maintaining the immunosuppressive state of tumor microenvironment (TME). High levels CD163+ TAMs specifically are associated with poor prognosis many solid types. Targeting may represent a key approach development next generation cancer immune therapeutics. Members leukocyte immunoglobulin-like receptor B (LILRB) family, including LILRB2 (ILT4), known to transmit inhibitory signals and other myeloid cells. Leveraging bulk single...
An effective cancer therapy requires killing cells and targeting the tumor microenvironment (TME). Searching for molecules critical multiple cell types in TME, we identified NR4A1 as one such molecule that can maintain immune suppressive TME. Here, establish a valid target immunotherapy describe first-of-its-kind proteolysis-targeting chimera (PROTAC, named NR-V04) against NR4A1. NR-V04 degrades within hours vitro exhibits long-lasting degradation tumors with an excellent safety profile....
Specific immune complexes, prepared at different ratios of antibody to antigen, were examined for their effects on the response BALB/c mice cell wall polysaccharide antigen (PnC) extracted from Streptococcus pneumonia R36a. Mice immunized with complexes formed in excess developed a PnC-specific that was equivalent injected free antigen. On other hand, very little antibody. Furthermore, administration (formed excess) resulted suppression an immunogenic dose PnC given concurrently or 1 day...
Abstract Mechanism of action studies are imperative for translating oncology therapeutics into the clinic informing testable hypotheses and potential combination partners. One class therapeutics, immune-stimulatory cytokines can augment antitumor efficacy checkpoint blockade, but further translational work is required to understand beneficial treatment effects versus unwanted immunotoxicities. SAR445877 (SAR’877, formerly KD050), a novel antibody-cytokine fusion protein consisting an Fc...
Abstract CAR T-cells have set a new standard of clinical activity in patients with hematologic malignancies but there are several barriers to broader patient access. Currently, the genetic modification patients' T cells produce CAR-T cell therapies is carried out ex vivo before infusing back into patient, using methods that complex and hinder widespread use. Here we share targeted lipid nanoparticle (LNP) encapsulating mRNA reprogram circulating human vivo, designed overcome significant...
Cancer cells can live and grow if they succeed in creating a favorable niche that often includes elements from the immune system. While T lymphocytes play an important role host response to tumor growth, mechanism of their trafficking remains poorly understood. We show here consistently infiltrate primary brain cancer, medulloblastoma. demonstrate, both vitro vivo, these are attracted deposits only after have interacted with vascular endothelium. Macrophage Migration Inhibitory Factor (MIF)"...
Interaction between lipoproteins and elastin in the arterial wall may play an important role atherosclerotic lipid deposition, but binding affinities other characteristics of interaction have not been determined previously. Elastin was isolated by hot alkali treatment human aortic tissue. At 4 degrees C, radioiodinated low density lipoprotein (LDL) bound to more than one class sites on elastin. Sites highest affinity had apparent dissociation constant 3.6 x 10(-8) M. Total at LDL...
An optimized antigen-presenting cell for tumor immunotherapy should produce a robust antigen specific cytotoxic T lymphocytes (CTL) response to tumor-associated antigens, which can persist in vivo and expand on reencounter. Interleukin (IL)-21 synergizes with other γ-chain cytokines enhance the frequency cytotoxicity of antigen-specific CTL. As cells themselves may serve as effective (T cells; TAPC) be useful cellular vaccines, we examined whether CD8+ genetically modified IL-21 could induce...
The primary antigen-specific antibody response of various strains mice to TEPC-15/PnC immune complexes has been examined. We found that both BALB/c and C3H were good responders the PnC antigen; however, low responders, whereas high complexes. Using congenic on background, we have shown is not restricted by gene products H-2 complex or Igh (allotype) locus. However, responsiveness may be controlled genes linked locus, since are Ighj, Ighd, Ighf Igha, Ighb, Ighe complex. Moreover, correlates...
Abstract Introduction: Immune checkpoint blockade (ICB) has revolutionized the treatment of many cancers, still most patients do not respond to PD-1 or CTLA-4 inhibitors. Thus, new Immuno-Oncology (IO) therapies that could potentially benefit non-responding are greatly needed. Jounce generated cell type-specific gene signatures as a means probing The Cancer Genome Atlas and other large datasets for novel IO targets. Regulatory T cells (Tregs) one attractive type targeting they may contribute...
Chimeric antigen receptors (CARs) are increasingly being used in clinical trials to treat a variety of malignant conditions and recent results with CD19-specific CARs showing complete tumor regressions has sparked the interest researchers public alike. Traditional have been generated using single-chain variable fragments (scFv), often derived from murine monoclonal antibodies, for specificity. As experience CAR T cells grows, so does potential unwanted immune responses against foreign...
Abstract Severe chronic active Epstein–Barr virus infection (CAEBV) in T or NK cells is a rare complication of latent EBV infection. CAEBV associated T‐cell lymphoproliferative disease (LPD) consists polyclonal lesions as well aggressive lymphomas. Here, we report such patient. In addition, show that this primary lymphoma expresses CD70 and sensitive to killing by CD70‐specific cells, identifying potential immunotherapeutic target for CAEBV‐associated lymphoma. Pediatr Blood Cancer...
Abstract During persistent viral infections and cancer, antigen-specific T cells become exhausted, express elevated levels of inhibitory receptors gradually lose their functional potential. Immune checkpoint blockade can restore function exhausted to result in tumor clearance, however, only a minority cancer patients see durable control. Immune-stimulatory cytokines augment the antitumor efficacy blockade, but clinical use is marred by substantial toxicity. SAR445877 (SAR’877, formerly...
Abstract Mechanism of action studies are imperative to translating oncology therapeutics into the clinic informing testable hypotheses and potential combination partners. This often involves large time-consuming mouse test a small number compounds in an attempt show statistically significant benefit. Likewise, testing multiple partners these systems is limited by time, cost, desire reduce animals used biological research. To overcome limitations, we utilized implantable microdevice (IMD)...