Development of alpha-gal conjugated anti-cancer antibodies

<none>

Programme Social programme Plenary speakers Keynote speakers 1st EuroCarb Young Researcher (ECYR) Workshop CarboMet Workshop Mini symposium: Glycobiology at the LUMC and beyond Favourites/Agenda

Social programme

Plenary speakers

Keynote speakers

1st EuroCarb Young Researcher (ECYR) Workshop

CarboMet Workshop

Mini symposium: Glycobiology at the LUMC and beyond

Favourites/Agenda

Photos

Venue & Travel Venue Accommodation City of Leiden Travel directions

Venue

Accommodation

City of Leiden

Travel directions

Committees

Home

Development of alpha-gal conjugated anti-cancer antibodies

Koichi Fukase 1 , Julinton Sianturi 1 , Yoshiyuki Manabe 1 , Hao-Sheng Li 1 , Li-Ting Chiu 2 , Tsung-Che Chang 1 , Kento Tokunaga 1 , Kazuya Kabayama 1 , Masahiro Tanemura 3 , Shinji Takamatsu 1 , Eiji Miyoshi 1 , Shang-Cheng Hung 2

1 Osaka University, Toyonaka, Japan, 2 Academia Sinica, Taipei, Taiwan, 3 Osaka Police Hospital, Osaka, Japan

Due to their excellent specificity, antibodies are among the most important molecular targeted drugs for various diseases. In this study, we developed α-gal antibody conjugates that dramatically increased cellular cytotoxicity by recruiting natural antibody through α-gal/anti-Gal antibody interaction [1].

α-Gal epitope (Galα1-3Galβ1-4GlcNAc-R) is expressed abundantly on glycolipids and glycoproteins in non-primate mammals, prosimians, and New World monkeys. Humans do not have α-gal due to inactivation of α-1,3-galactosyltransferase. Instead, they make large quantities of anti-Gal antibodies, which specifically interact with α-gal. Anti-Gal antibodies are the most abundant natural antibodies found in humans (1–2% of total serum IgG and 3–8% of total IgM). Consequently, α-gal antigen causes an acute immune response. α-Gal/anti-Gal antibodies interaction following xenotransplantation from pig to baboon induced hyperacute rejection of the transplanted tissues.

In this study, we applied the ADC (antibody-drug conjugate) concept to develop a novel α-gal-based tumor immunotherapy. Because α-gal antigen causes an extremely strong immune response, anti-tumor antibodies conjugated with α-gal was expected to have high potency against tumors.

After chemical synthesis of α-gal, we achieved concise chemical conjugation of antibodies with α-gal. The synthesized α-gal antibody conjugates efficiently provoked an immune response. The potency of α-gal antibody conjugates depended on the α-gal loading ratio. The larger the amount of α-gal was introduced, the higher the cytotoxicity was observed. Utilization of α-gal dendrimer allowed introduction of large amounts of α-gal epitope to the antibody without loss of affinity for the target cell. The method described here will enable re-development of antibodies to improve their potency.

Strategy for tumor immunotherapy using α-gal antibody conjugate.

Sianturi J, Manabe Y, Li HS, Chiu LT, Chang TC, Tokunaga K, Kabayama K, Tanemura M, Takamatsu S, Miyoshi E, Hung SC, Fukase K. Development of α-Gal Antibody Conjugates for Increasing Immune Response by Recruiting Natural Antibodies. Angew Chem Int Ed Engl. 2019. doi: 10.1002/anie.201812914 .

Contact eurocarb@eurocarb2019.com for general questions about EUROCARB2019, or codee@eurocarb2019.com for scientific questions.

Leiden University / Leiden Institute of Chemistry lic.leidenuniv.nl

European Carbohydrate Organisation

Congress by Design www.congressbydesign.com