Publicação
TRIFECTA - Development of a novel trispecific antibody for the anticancer immune targeting of non-Hodgkin Lymphoma
| datacite.subject.fos | Departamento de Biologia Vegetal | pt_PT |
| dc.contributor.advisor | Amaral, Joana São José Dias, 1979- | |
| dc.contributor.advisor | Carlos, Ana Rita Cabral Martins, 1985- | |
| dc.contributor.author | Rosa, Inês Pessanha | |
| dc.date.accessioned | 2025-02-03T17:25:57Z | |
| dc.date.embargo | 2028-02-23 | |
| dc.date.issued | 2025 | |
| dc.date.submitted | 2024 | |
| dc.description | Tese de mestrado, Biologia Molecular e Genética , 2025, Universidade de Lisboa, Faculdade de Ciências | pt_PT |
| dc.description.abstract | Non-Hodgkin Lymphoma (NHL) is among leading causes of cancer-related death worldwide, although prognosis has improved in recent years. Several innovative drugs are in clinical development for NHL treatment; however, approvals remain limited, partly due to the lack of clinically relevant models for validation. Immunotherapy strategies have been developed; however, the high pace of clinical application present challenges, highlighting the need for novel strategies and models for developing successful and cost-effective immunotherapies. Due to its similarity to human disease, the canine lymphoma model has been suggested as a powerful tool for translating novel immunotherapies into clinical practice. A promising approach to optimize immunotherapy involves the development of bispecific antibodies that simultaneously bind to cancer cells and recruit T-lymphocytes, redirecting and unleashing T-lymphocytes cytotoxicity against cancer cells. However, by engaging the TCR/CD3 complex alone, most bispecific antibodies lead to T-lymphocytes activation and faster exhaustion. This project aimed to develop a trispecific antibody (TsAb) targeting CD20 receptor, overexpressed in B-lymphocytes malignancies, and CD3 and CD28 receptors on T-lymphocytes. Targeting CD3 activates Tlymphocytes, while targeting CD28 supports long-lasting T-lymphocytes proliferation by supplying a co-stimulatory signal that activates an alternate signal transduction pathway and inhibits apoptosis. For that purpose, TsAb targeting canine CD20, CD3, and CD28 was engineered, produced, and purified. Optimization of canine T-lymphocyte isolation was conducted for in vitro assays evaluating TsAb’s ability to promote T- lymphocyte activation and canine NHL cell cytotoxicity. A Phage Display selection was carried out on a rabbit single domain (sdAb) antibody library, identifying antibodies specific to canine CD3. ELISA screening allowed the selection of sdAbs with promising expression and binding properties, which could be integrated into improved TsAb in the future. Overall, this project supports the development of next-generation T- lymphocytes engager antibodies for cancer treatment, while providing realistic opportunities for clinical translation. | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.5/98060 | |
| dc.language.iso | eng | pt_PT |
| dc.subject | Linfoma | pt_PT |
| dc.subject | Imunoterapia | pt_PT |
| dc.subject | Anticorpo Triespecífico | pt_PT |
| dc.subject | Phage Display | pt_PT |
| dc.subject | CD3 | pt_PT |
| dc.subject | Teses de mestrado - 2025 | pt_PT |
| dc.title | TRIFECTA - Development of a novel trispecific antibody for the anticancer immune targeting of non-Hodgkin Lymphoma | pt_PT |
| dc.type | master thesis | |
| dspace.entity.type | Publication | |
| rcaap.rights | embargoedAccess | pt_PT |
| rcaap.type | masterThesis | pt_PT |
| thesis.degree.name | Tese de mestrado em Biologia Molecular e Genética | pt_PT |