A5029769755- CAR-T cell therapy research
- Peptidase Inhibition and Analysis
- Melanoma and MAPK Pathways
- Synthesis and Biological Evaluation
- Bladder and Urothelial Cancer Treatments
- Synthesis of Tetrazole Derivatives
- melanin and skin pigmentation
- Cancer Research and Treatments
- Immunotherapy and Immune Responses
- Autophagy in Disease and Therapy
- Cancer Immunotherapy and Biomarkers
- Gut microbiota and health
- Cancer, Hypoxia, and Metabolism
- Signaling Pathways in Disease
- Cutaneous Melanoma Detection and Management
- Epigenetics and DNA Methylation
- Calcium signaling and nucleotide metabolism
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- ATP Synthase and ATPases Research
- Synthesis and biological activity
- Estrogen and related hormone effects
- Cancer, Lipids, and Metabolism
- Biochemical and Molecular Research
University of Pennsylvania
2018-2024
Universitat Autònoma de Barcelona
2013-2022
Abramson Cancer Center
2020
Abstract Clinical trials repurposing lysosomotropic chloroquine (CQ) derivatives as autophagy inhibitors in cancer demonstrate encouraging results, but the underlying mechanism of action remains unknown. Here, we report a novel dimeric CQ (DC661) capable deacidifying lysosome and inhibiting significantly better than hydroxychloroquine (HCQ). Using an situ photoaffinity pulldown strategy, identified palmitoyl-protein thioesterase 1 (PPT1) molecular target shared across monomeric derivatives....
Abstract The desmoplastic stroma in solid tumors presents a formidable challenge to immunotherapies that rely on endogenous or adoptively transferred T cells, however, the mechanisms are poorly understood. To define involved, here we treat established pancreatic with CAR cells directed fibroblast activation protein (FAP), an enzyme highly overexpressed subset of cancer-associated fibroblasts (CAFs). Depletion FAP + CAFs results loss structural integrity matrix. This renders these...
The use of lipid nanoparticles (LNP) to encapsulate and deliver mRNA has become an important therapeutic advance. In addition vaccines, LNP-mRNA can be used in many other applications. For example, targeting the LNP with anti-CD5 antibodies (CD5/tLNP) allow for efficient delivery payloads T cells express protein. As percentage protein expressing induced by intravenous injection CD5/tLNP is relatively low (4-20%), our goal was find ways increase mRNA-induced translation efficiency. We showed...
Abstract Resistance to BRAF and MEK inhibitors (BRAFi + MEKi) in BRAF-mutant tumors occurs through heterogeneous mechanisms, including ERK reactivation autophagy. Little is known about the mechanisms by which or autophagy induced BRAFi MEKi. Here, we report that melanoma cells, MEKi SEC61-dependent endoplasmic reticulum (ER) translocation of MAPK pathway via GRP78 KSR2. Inhibition ER prevented Following translocation, exited was rephosphorylated PERK. Reactivated phosphorylated ATF4,...
Chimeric antigen receptor (CAR) T cells demonstrate remarkable success in treating hematological malignancies, but their effectiveness non-hematopoietic cancers remains limited. This study proposes enhancing CAR cell function and localization solid tumors by modifying the epigenome governing tissue-residency adaptation early memory differentiation. We identify that a key factor human tissue-resident (CAR-T
New strategies are needed to enhance the efficacy of anti–programmed cell death protein antibody (anti–PD-1 Ab) in cancer. Here, we report that inhibiting palmitoyl-protein thioesterase 1 (PPT1), a target chloroquine derivatives like hydroxychloroquine (HCQ), enhances antitumor anti–PD-1 Ab melanoma. The combination resulted tumor growth impairment and improved survival mouse models. Genetic suppression core autophagy genes, but not Ppt1, cancer cells reduced priming cytotoxic capacity...
Despite the success of chimeric antigen receptor (CAR) T-cell therapy against hematologic malignancies, successful targeting solid tumors with CAR T cells has been limited by a lack durable responses and reports toxicities. Our understanding therapeutic efficacy in could be improved quantitative tools that allow characterization T-targeted antigens accurate monitoring response.
The rough morphotypes of non-tuberculous mycobacteria have been associated with the most severe illnesses in humans. This idea is consistent fact that Mycobacterium tuberculosis presents a stable morphotype. Unlike smooth morphotypes, bacilli grow close together, leaving no spaces among them and forming large aggregates (clumps). Currently, initial interaction macrophages clumps remains unclear. Thus, we infected J774 bacterial suspensions abscessus containing primarily isolated bacilli....
Mycobacterium bovis bacillus Calmette-Guérin is the most effective treatment for high risk noninvasive bladder cancer. Although immunotherapy clearly decreases recurrence and progression rates, side effects are common infection with has been described. For these reasons it necessary to find safer alternatives live bacillus. We explored possibility of using killed but metabolically active Calmette-Guérin.T24, J82 RT4 tumor cell lines were cultured irradiation or heat treated Connaught....
Abstract The hydrophobic composition of mycobacterial cell walls leads to the formation clumps when attempting resuspend mycobacteria in aqueous solutions. Such aggregation may interfere mycobacteria-host cells interaction and, consequently, influence their antitumor effect. To improve immunotherapeutic activity Mycobacterium brumae , we designed different emulsions and demonstrated efficacy. best formulation was initially selected based on homogeneity stability. Both olive oil (OO)- mineral...
No AccessJournal of UrologyInvestigative Urology1 Jan 2016γ Irradiated Mycobacteria Enhance Survival in Bladder Tumor Bearing Mice Although Less Efficaciously than Live Estela Noguera-Ortega, Rosa Maria Rabanal, Silvia Secanella-Fandos, Eduard Torrents, Marina Luquin, and Esther Julián Noguera-OrtegaEstela Noguera-Ortega Departament de Genètica i Microbiologia, Facultat Biociències, Universitat Autònoma Barcelona, Spain , RabanalRosa Rabanal Unitat Patologia Murina Comparada, Medicina...
The standard treatment for high-risk non-muscle invasive bladder cancer (BC) is the intravesical administration of live Mycobacterium bovis BCG. Previous studies suggest improving this therapy by implementing non-pathogenic mycobacteria, such as brumae, and/or different vehicles mycobacteria delivery, an olive oil (OO)-in-water emulsion. While it has been established that BCG activates immune system, effects altering mycobacterium preparation remain unknown. In orthotopic murine BC model,...
The mechanism of action intravesical Mycobacterium bovis BCG immunotherapy treatment for bladder cancer is not completely known, leading to misinterpretation BCG-unresponsive patients, who have scarce further therapeutic options. grown under diverse culture conditions worldwide, which can impact the antitumor effect strains and could be a key parameter success. Here, nonpathogenic brumae were in four media currently used by research laboratories manufacturers: Sauton-A60, -G15 -G60...
The desmoplastic stroma in solid tumors presents a formidable challenge to immunotherapies that rely on endogenous or adoptively transferred T cells, however, the mechanisms are poorly understood. To define involved, we treat established pancreatic with CAR cells directed fibroblast activation protein (FAP), an enzyme highly overexpressed subset of cancer-associated fibroblasts (CAFs). Depletion FAP+CAFs results loss structural integrity matrix. This renders these treatment-resistant cancers...
Abstract Cancer-associated fibroblasts (CAFs) support tumor growth and metastasis of virtually all solid tumors, making them a potential “universal therapeutic target.” However, there are challenges to designing CAF targeted therapies. First, CAFs heterogeneous, consisting tumor-promoting tumor-restraining populations. Second, molecular targets expressed strictly by have yet be defined. Nonetheless, Fibroblast Activation Protein (FAP) is selectively overexpressed on CAFs. Moreover, deleting...
Supplementary Data from Monitoring Therapeutic Response to Anti-FAP CAR T Cells Using [<sup>18</sup>F]AlF-FAPI-74