Thesis defense: Biagio Todaro

on the December 9, 2020

December 9, 10:00 am
Biagio Todaro from DCM will defend his thesis entitled: "Engineering of biomolecular systems for anti-tumoral immunotherapy".
The Antibody Recruiting Molecules (ARMs) belong to the promising alternative in immunotherapy against cancer and pathogens. In the tumoral contest, an ARM has the singular ability to interface between the target cell and components of the immune system present on the environment leading to an immune response. In this Ph.D. work, we reported the design and the synthesis by click chemistry of several ARMs able to target over-expressed proteins on cancer cell surface through peptides-based tumoral binding modules (TBMs) and to engage natural endogenous antibodies through carbohydrate-based antibody binding modules (ABMs). Next, we demonstrated the formation of a ternary complex between cell-ARM-antibodies and the specific killing of cancer cells by our agents only in the presence of human serum as unique source of immune effectors, without pre-immunization. In addition, we established that the molecule flexibility, the length of the linker between ABM and TBM, the nature of the haptens (carbohydrates and peptides) and their valency play a significant role. Due to the efficiency of the synthetic process, a large diversity of ARMs could be easily created, opening new outlooks in diverse therapeutic fields.
Key words
Antibody Recruiting Molecules (ARMs), cancer immunotherapy, click chemistry, multivalency, flow cytometry, cell-based cytotoxicity assay.
Published on November 26, 2020

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