Journal article
Live-attenuated LCMV-based vector for active immunotherapy of HPV16+ cancer.
- Schmidt, Sarah Hookipa Pharma Inc., New York, NY;
- Bonilla, Weldy V. Department of Biomedicine-Division of Experimental Virology, University of Basel, Basel, Switzerland;
- Pauzuolis, Mindaugas Department of Pathology and Immunology, Geneva, Switzerland;
- Reiter, Andrea Hookipa Pharma Inc., New York, NY;
- Kleissner, Theresa Hookipa Pharma Inc., New York, NY;
- Oeler, Daniel Hookipa Pharma Inc., New York, NY;
- Stemeseder, Felix Hookipa Pharma Inc., New York, NY;
- Berka, Ursula Hookipa Pharma Inc., New York, NY;
- Kiefmann, Bettina Hookipa Pharma Inc., New York, NY;
- Schulha, Sophie Hookipa Pharma Inc., New York, NY;
- Matushansky, Igor Hookipa Pharma Inc., New York, NY;
- Merkler, Doron Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland;
- Pinschewer, Daniel Department of Biomedicine-Division of Experimental Virology, University of Basel, Basel, Switzerland;
- Orlinger, Klaus Karl HOOKIPA Pharma Inc, New York, NY;
Published in:
- Journal of Clinical Oncology. - American Society of Clinical Oncology (ASCO). - 2019, vol. 37, no. 15_suppl, p. e14303-e14303
English
e14303 Background: Active immunization against cancer requires the induction of exquisitely potent tumor-specific CD8+ T cell (CTL) responses, which can be repeatedly boosted and reactivated. Hookipa Pharma engineered a replication-attenuated viral vector platform (TheraT) based on the arenavirus lymphocytic choriomeningitis virus (LCMV), which meets these aforementioned criteria. Here, we present a preclinical data package of Hookipa´s lead immunotherapy product HB-201, targeting HPV16-driven cancer. Methods: TheraT-E7E6 encodes a highly immunogenic, non-oncogenic version of the human papilloma virus 16 (HPV16) oncoproteins E7 and E6. Results: Attenuation and safety of TheraT-E7E6 were demonstrated by i) rapid viral clearance after systemic administration of the vector and ii) reduced neurovirulence in mice.TheraT-E7E6 can be administered intravenously as systemic therapy or intratumorally as local therapy with an abscopal-like effect. Treatment was shown to induce substantial CD8+ T cell expansion and high frequencies of E7- and E6-specific CTL responses with a balanced effector / central memory profile. These responses were boosted and reactivated upon TheraT-E7E6 re-administration. TheraT-E7E6 eradicated palpable tumors in a syngeneic mouse TC-1 tumor model of HPV-driven cancer. Even in mice with large tumors (~300mm3 ) TheraT-E7E6 afforded significant tumor control and improved survival, with high frequencies of E7-specific CTLs persisting for several weeks. Animals which cleared the tumor after TheraT therapy were long term protected from tumor re-challenge. Furthermore, TheraT is efficacious in checkpoint inhibitory refractory models and can also synergize in combination with checkpoint inhibitors (CPIs). Conclusions: In conclusion, replication-attenuated TheraT-E7E6 is safe, highly immunogenic and shows excellent therapeutic efficacy as mono- or combination therapy in a preclinical model of HPV-induced cancer. Clinical trials for the treatment of HPV16+ cancers will be initiated in 2019.
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1200/jco.2019.37.15_suppl.e14303
- ISSN 0732-183X
- Persistent URL
- https://sonar.ch/global/documents/252069
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