A5058309507- CAR-T cell therapy research
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Pluripotent Stem Cells Research
- Nanowire Synthesis and Applications
- Genetics, Aging, and Longevity in Model Organisms
- MicroRNA in disease regulation
- Extracellular vesicles in disease
- Immune Cell Function and Interaction
- Nanoplatforms for cancer theranostics
- Immunotherapy and Immune Responses
Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research
2018-2024
Abstract Background Active targeting by surface-modified nanoplatforms enables a more precise and elevated accumulation of nanoparticles within the tumor, thereby enhancing drug delivery efficacy for successful cancer treatment. However, surface functionalization involves complex procedures that increase costs timelines, presenting challenges clinical implementation. Biomimetic (BNPs) have emerged as unique platforms overcome limitations actively targeted nanoparticles. Nevertheless, BNPs...
Anti-CD19 chimeric antigen receptor (CAR)-T cells have achieved impressive outcomes for the treatment of relapsed and refractory B-lineage neoplasms. However, important limitations still remain due to severe adverse events (i.e., cytokine release syndrome neuroinflammation) relapse 40%-50% treated patients. Most CAR-T are generated using retroviral vectors with strong promoters that lead high CAR expression levels, tonic signaling, premature exhaustion, overstimulation, reducing efficacy...
Autologous T cells expressing the Chimeric Antigen Receptor (CAR) have been approved as advanced therapy medicinal products (ATMPs) against several hematological malignancies. However, generation of patient-specific CAR-T delays treatment and precludes standardization. Allogeneic off-the-shelf are an alternative to simplify this complex time-consuming process. Here we investigated safety efficacy knocking out TCR molecule in ARI-0001 cells, a second αCD19 CAR by Spanish Agency Medicines...
Controlling transgene expression through an externally administered inductor is envisioned as a potent strategy to improve safety and efficacy of gene therapy approaches. Generally, inducible ON systems require chimeric transcription factor (transactivator) that becomes activated by inductor, which not optimal for clinical translation due their toxicity. We generated previously the first all-in-one, transactivator-free, doxycycline (Dox)-responsive (Lent-On-Plus or LOP) lentiviral vectors...
Integration-defective lentiviral vectors (IDLVs) have become an important alternative tool for gene therapy applications and basic research. Unfortunately, IDLVs show lower transgene expression as compared to their integrating counterparts. In this study, we aimed improve the levels of by inserting IS2 element, which harbors SARs HS4 sequences, into LTRs (SE-IS2-IDLVs). Contrary our expectations, presence element did not abrogate epigenetic silencing histone deacetylases. addition, reduced...
Integration-deficient lentiviral vectors (IDLVs) have recently generated increasing interest, not only as a tool for transient gene delivery, but also technique detecting off-target cleavage in gene-editing methodologies which rely on customized endonucleases (ENs). Despite their broad potential applications, the efficacy of IDLVs has historically been limited by low transgene expression and reduced sensitivity to detect low-frequency events. We previously reported that incorporation...
ABSTRACT Background Chimeric antigen receptor (CAR) T cells directed against CD19 have achieved impressive outcomes for the treatment of relapsed/refractory B lineage lymphoid neoplasms. However, CAR-T therapy still has important limitations due to severe side effects and lack efficiency in 40-50% patients. Most CARs-T products are generated using retroviral vectors with strong promoters. high CAR expression levels can lead tonic signalling, premature exhaustion over-stimulation cells,...
Abstract Background Despite their success treating type B cancers, Chimeric Antigen Receptor (CAR) T cells still showed limited efficacy in certain lymphomas and solid tumors. Reinforcing conventional CAR-T to release cytokines can improve but also increase safety concerns. Several strategies have been developed regulate secretion using minimal promoters that are controlled by chimeric proteins harboring transactivators. However, these disrupt the normal physiology of target cells. Methods...
In spite of the enormous potential CRISPR/Cas in basic and applied science, levels undesired genomic modifications cells still remain mostly unknown controversial. Nowadays, efficiency specificity cuts generated by is main concern. However, there are also other drawbacks when DNA donors used for gene repair or knock-ins. These GE strategies should take into account not only nucleases, but fidelity donor to carry out their function. The current methods quantify costly lack sensitivity detect...