Antonio J. Almazan
A5082515649- CAR-T cell therapy research
- Cardiac, Anesthesia and Surgical Outcomes
- Pancreatic and Hepatic Oncology Research
- Amoebic Infections and Treatments
- Hepatitis C virus research
- Infective Endocarditis Diagnosis and Management
- Chronic Lymphocytic Leukemia Research
- Central Venous Catheters and Hemodialysis
- Bacterial Identification and Susceptibility Testing
- Public Health and Environmental Issues
- Phagocytosis and Immune Regulation
- Rabies epidemiology and control
- Protein Degradation and Inhibitors
- Surgical site infection prevention
- Liver Disease Diagnosis and Treatment
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Anesthesia and Pain Management
- Nanoplatforms for cancer theranostics
- Nosocomial Infections in ICU
- HIV/AIDS drug development and treatment
- Tryptophan and brain disorders
- Appendicitis Diagnosis and Management
- Pneumocystis jirovecii pneumonia detection and treatment
- Immune Cell Function and Interaction
Massachusetts General Hospital
2023-2024
Harvard University
2024
Santa Lucía University General Hospital
2012
Targeting solid tumors with chimeric antigen receptor (CAR) T cells remains challenging due to heterogenous target expression, escape, and the immunosuppressive tumor microenvironment (TME). Pancreatic cancer is characterized by a thick stroma generated cancer-associated fibroblasts (CAF), which may contribute limited efficacy of mesothelin-directed CAR in early-phase clinical trials. To provide more favorable TME for pancreatic ductal adenocarcinoma (PDAC), we an antimesothelin secreted...
Abstract Chimeric Antigen Receptor (CAR) T cells directed to B cell maturation antigen (BCMA) mediate profound responses in patients with multiple myeloma, but most do not achieve long-term complete remissions. In addition, recent evidence suggests that high-affinity binding BCMA can result on-target, off-tumor activity the basal ganglia and lead fatal Parkinsonian-like disease. Here we develop CAR against myeloma using a binder targeting transmembrane activator CAML interactor (TACI) mono...
Persisters are a sub-population of tumor cells that survive anti-cancer therapy facilitating recurrence, and have been identified following drug- immune-therapy but generally considered as distinct entities. Drugs immune often kill via apoptosis, therefore, we tested hypothesis both types based on reduced mitochondrial apoptotic sensitivity, which would yield multi-therapy resistance. We observed IPCs acquired sensitivity to multiple drugs radiotherapy. Likewise, DTPs developed radiotherapy,...
<p>Supplementary Video S2. Meso^FAP CAR T cells on AsPC1</p>
<p>Supplementary Methods</p>
<p>Supplementary Figure S8. Target expression and individual analysis of patient-derived organoids (PDO) with matching CAFs.</p>
<p>Supplementary Figure S6. Human CAF-1 cells do not expand in vivo NSG mice the presence or absence of AsPC-1 PDX1294 cells.</p>
<p>Supplementary Figure S5. Intratumoral multiplex RNA-ISH IF imaging and analysis of CAR-TEAM treated mice.</p>
<p>Supplementary Figure S3. ASPC-1 and CAF repeat stimulation initiates a different transcription profile of meso^FAP meso^CD19 CAR T-cells over time.</p>
<p>Supplementary Video S9. UTD T cells on AsPC1 + CAF</p>
<p>Supplementary Video S1. Meso^FAP CAR T cells on AsPC1 + CAF</p>
<div>AbstractPurpose:<p>Targeting solid tumors with chimeric antigen receptor (CAR) T cells remains challenging due to heterogenous target expression, escape, and the immunosuppressive tumor microenvironment (TME). Pancreatic cancer is characterized by a thick stroma generated cancer-associated fibroblasts (CAF), which may contribute limited efficacy of mesothelin-directed CAR in early-phase clinical trials. To provide more favorable TME for pancreatic ductal adenocarcinoma...
<p>Supplementary Figure S1. Characterization of mesoFAP CAR T-cells compared to control T-cells.</p>
<p>Supplementary Figure S6. Human CAF-1 cells do not expand in vivo NSG mice the presence or absence of AsPC-1 PDX1294 cells.</p>
<p>Supplementary Figure S7. Superior anti-tumor effect of meso^FAP compared to the combination meso-CAR and FAP-CAR or meso^CD19.</p>
<p>Supplementary Figure S4. Still frames from live cell microscopy videos demonstrating reduced edge dynamics of meso^FAP CAR T-cells compared to controls and target layer on flow chamber acoustic microscopy.</p>
<p>Supplementary Video S11. UTD T cells on CAF</p>
<p>Supplementary Figure S2. In vitro setup of CARTEAM to CAF:AsPC-1 with different ratios showing superiority mesoFAP compared CARs targeting mesothelin only.</p>
<p>Supplementary Video S12. UTD T cells not on target</p>
<p>Supplementary Video S4. Meso^FAP CAR T cells not on target</p>
<p>Supplementary Video S6. Meso^CD19 CAR T cells on AsPC1</p>