Oana Hangiu
A5034999583- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Radiopharmaceutical Chemistry and Applications
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Glycosylation and Glycoproteins Research
- Multiple Myeloma Research and Treatments
Research Institute Hospital 12 de Octubre
2021-2025
Hospital Universitario 12 De Octubre
2022-2025
Multiple myeloma is the second most common hematological malignancy in adults and remains an incurable disease. B cell maturation antigen (BCMA)–directed immunotherapy, including T cells bearing chimeric receptors (CARs) systemically injected bispecific engagers (TCEs), has shown remarkable clinical activity, several products have received market approval. However, despite promising results, patients eventually become refractory relapse, highlighting need for alternative strategies....
Immune checkpoint inhibitors have revolutionized cancer therapy, but many patients fail to respond or develop resistance, often due reduced T cell activity. Costimulation via 4-1BB has emerged as a promising approach enhance the effector function of antigen-primed cells. Bispecific cell-engaging (TCE) antibodies are an effective way provide tumor-specific receptor-mediated signaling tumor-infiltrating lymphocytes. mRNA-based delivery bispecific antibodies, offer novel immune responses while...
Immune checkpoint blockade (ICB) with antibodies has shown durable clinical responses in a wide range of cancer types, but the overall response rate is still limited. Other effective therapeutic modalities to increase ICB rates are urgently needed. New bispecific antibody (bsAb) formats combining effect and direct action on cells could improve efficacy current immunotherapies. Here, we report development PD-L1/EGFR symmetric bsAb by fusing dual-targeting tandem trimmer body human IgG1 hinge...
Abstract Purpose: The induction of 4-1BB signaling by agonistic antibodies can drive the activation and proliferation effector T cells thereby enhance a T-cell–mediated antitumor response. Systemic administration anti-4-1BB–agonistic IgGs, although effective preclinically, has not advanced in clinical development due to their severe hepatotoxicity. Experimental Design: Here, we generated humanized EGFR-specific 4-1BB-agonistic trimerbody, which replaces IgG Fc region with human collagen...
The dismal clinical outcome of relapsed/refractory (R/R) T cell acute lymphoblastic leukemia (T-ALL) highlights the need for innovative targeted therapies. Although chimeric antigen receptor (CAR)-engineered cells have revolutionized treatment B malignancies, their implementation in T-ALL is its infancy. CD1a represents a safe target cortical (coT-ALL) patients, and fratricide-resistant CD1a-directed CAR been preclinically validated as an immunotherapeutic strategy R/R coT-ALL. Nonetheless,...
Costimulation of tumor-infiltrating T lymphocytes by anti-4-1BB monoclonal antibodies (mAbs) has shown anti-tumor activity in human trials, but can be associated with significant off-tumor toxicities involving FcγR interactions. Here, we introduce albumin-fused mouse and bispecific clinically favorable pharmacokinetics designed to confine 4-1BB costimulation the tumor microenvironment. These Fc-free agonists consist an EGFR-specific VHH antibody, a 4-1BB-specific scFv, albumin sequence...
LEAD-452 is a humanized bispecific EGFR-targeted 4-1BB-agonistic trimerbody with unique trimeric configuration compared to other 4-1BB-specific antibodies that are currently in development. Indeed, enhanced tumor-specific costimulation and very remarkable safety efficacy profiles have been observed mouse models. Here, we conducted for the first time preclinical pharmacokinetic toxicity study non-human primates (NHP) (Macaca fascicularis). exhibits comparable binding affinity human macaque...
Immune checkpoint blockade has changed the treatment paradigm for advanced solid tumors, but overall response rates are still limited. The combination of with anti-4-1BB antibodies to stimulate tumor-infiltrating T cells shown anti-tumor activity in human trials. However, further clinical development these been hampered by significant off-tumor toxicities. Here, we generated an anti-4-1BB/EGFR/PD-L1 trispecific antibody consisting a triple-targeting tandem trimerbody (TT) fused engineered...
<p>Supplementary Material and Methods</p>
<p>Pharmacokinetic parameters.</p>
<p>Effect of 4-1BBN/CEGFR trimerbody on EGFR-mediated signaling</p>
<p>Representative images of CD3+ and FoxP3+ TIL immunostaining</p>
<p>Analysis by SAXS of the arrangement in solution 4-1BBN trimerbody.</p>
<p>Binding of 4-1BBN/CEGFR to cell surface expressed hu4-1BB and huEGFR.</p>
<p>Oligonucleotides used in this study</p>
<p>Commercial antibodies</p>
<p>Kinetic constants</p>
<p>Species specificity of the 4-1BBN/CEGFR trimerbody.</p>
<p>Schematic diagrams showing the protein structure of anti-hu4-1BB IgG (a), and gene layout (b) (c) trimerbody.</p>
<p>SAXS Data Collection and derived parameters</p>
<p>Co-stimulatory activity of control antibodies.</p>
<p>Recombinant antibodies</p>
<p>Serum stability of the 4-1BBN/CEGFR trimerbody.</p>
<p>Co-stimulation studies in primary human cells</p>
<p>Binding assays of 4-1BB IgG and urelumab.</p>