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To discuss scientific and commercial issues around regulation, manufacturing, partnering, trails in the field of pharma, join the leading experts at pharma conferences 2017.

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Blanka Rihova

Speaker for Pharmaceutical Conferences-Blanka Rihova

Title: HPMA copolymer-bound doxorubicin as endogenous vaccine substantially increases therapeutic effect of check-point blockage monoclonals: Acute versus chronic model

Blanka Rihova

Institute of Molecular Genetics of the ASCR, Czech Republic

Biography

Blanka Rihova is Professor of Immunology, Charles University, Prague, Czech Republic and Adjunct Professor of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah, USA. In 2000 – 2007 she was a director of the Institute of Microbiology, Academy of Sciences of the Czech Republic. She is president of Czech Immunology Society, vice-president of Czech Learned Society and a member of Scientific Council of the Academy of Sciences of the Czech Republic. In 2009 she served as European Ambassador for Creativity and Innovation. She was awarded with Laurel Medal from Czech Chamber of Commerce, Medal from Czech Learned Society (Societas Scientiarum Bohemica “Ad Laudem et Honorem”), Medal of the Senate of the Parliament of the Czech Republic, Medal of the Academy of Sciences of the Czech Republic “De scientia et humanitate optime meritis”, “Garnet Immunoglobulin” from Czech Immunological Society, Medal of the “Czech Head”, award for the invention in the field of polymeric drugs etc. Recently, she is mainly involved in development of targeted cytostatic drugs and anticancer immune response.

Abstract

DOXHYD-HPMA is doxorubicin bound through hydrazone bond to synthetic polymeric carrier based on N-(2-hydroxypropyl)methacrylamide. It is effective anticancer polymeric prodrug with decreased side-toxicity and the ability to induce immunogenic cancer cell death releasing site-specific tumor antigen and thus acting as endogenous vaccine. We have compared chemo-immunotherapy combination treatment of EL4 T cell lymphoma and 4T1 breast carcinoma with DOXHYD-HPMA and with immune checkpoint blocking anti-CTLA-4 and anti-PD-1 MABs either alone or in a mixture. To document the role of intestinal microbiota we use germ-free (GF) mice and GF mice monocolonized with Bifidobacterium thetaiotamicron. Acute model of disease when mice are transplanted once with a lethal dose of tumor cells was compared with chronic model where mice are injected six times every other day with a low number of tumor cells. Healthy mice treated with anti-CTLA-4 and anti-PD-1 mAbs did not show any signs of toxicity while significant co-toxicity was seen in cancer-bearing mice. Treatment with checkpoint inhibitors exerted only a very limited cancer response as no long term survivors (LTS) were recorded. On the other hand more than 60% of mice injected also with therapeutically suboptimal dose of DOXHYD-HPMA survived disease-free for more than 100 days. Those suffering from chronic model of cancer showed considerably higher proportion of PD-1+ cells in tumor microenvironment and reacted substantially better to anti-CTLA-4 or anti-PD-1 treatment than mice with the acute model.