New insights into replicating viral vector platform

8th June 2018

Hookipa Biotech, a clinical stage biotech company pioneering an innovative class of active immunisation therapies for oncology and infectious diseases, has announced the publication of a new preclinical study of its TheraT replicating viral platform in the journal Immunity.

The study was led by Professor Doron Merkler, M.D., and his team at the Department of Pathology and Immunology at the University of Geneva, Switzerland. CD8+ cytotoxic T lymphocytes (CTLs) are important in the body's defence against infection and cancer and, in addition, contribute to the pathogenesis of several autoimmune diseases. In this study a mouse model of central nervous system autoimmune disease was used to investigate how priming by distinct microbes may enable CTLs to destroy self-tissues.

The study demonstrated that TheraT-induced CD8+ T cells have a unique transcriptional profile, characterised by expression of the master transcription factor thymocyte selection-associated HMG-box protein (TOX). TOX expression unleashes the tissue-destructive potential of CD8+ T cells by repressing the immune checkpoint 2B4/CD244. Expression of TOX, which is selectively induced by TheraT, enables CD8+ T cells to establish long-lasting interactions with their target cells inside solid tissues and kill them.

Professor Daniel D. Pinschewer, M.D., Hookipa's Chief Scientific Officer and a co-author of the paper, said, "This data is very encouraging. It shows that TOX expression enables TheraT-induced CD8+ T cells to attack and destroy "self" tissue. A limitation of other immunisation approaches has been that cancer also being a 'self' tissue avoids immune mediated destruction. This feature of TheraT-induced CD8+ T cells is of paramount importance in the immune response against cancer, which in essence represents an autoimmune attack that is desired and beneficial to the patient as it is directed specifically to and effective against the cancer.

Joern Aldag, Hookipa's Chief Executive Officer added, "Eliciting a potent T cell response is vital to treating patients with some of the most aggressive types of cancer. These novel findings by the Merkler group build on previously published data on our platform and provide additional mechanistic insights highlighting why TheraT represents a uniquely potent approach, capable of turning Œcold tumours hot."

Hookipa is performing IND-enabling studies for HB-201/TheraT to be tested in human papillomavirus positive (HPV+) head and neck squamous cell carcinoma. A Phase 1 trial is scheduled to start in 2019 as a monotherapy. In 2020, HB-201 will be combined with a checkpoint inhibitor and later with HB-202, a complementary TheraT-based product in preclinical development.





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