https://forskningsprosjekter.ihelse.net/prosjekt/46056834
Utdrag:
2017 - sluttrapport
Impaired anti-mycobacterial T cell functions in HIV-infected patients
The main aim of this research project was to improve our understanding of immune functions in HIV-infected individuals and how we can use this knowledge to develop new treatment strategies. Main achievements in this project: Establishment of HIV virus laboratory work protocols. The project developed procedures and BSL3 laboratory routines to perform HIV virus research work at NTNU/CEMIR. This includes methods to propagate, purify and quantify HIV as well as different HIV infections models for T cell lines and primary T cells. HIV laboratory tools were previously not available at our institute. These methods will also be used in future studies, for example in a recently performed CRISPR/Cas9 whole genome screen for HIV resistance and susceptibility genes (collaboration R. Kandasamy, CEMIR). Such studies are important to identify new targets in order to develop new treatment strategies for HIV. Discovery that HIV infection stimulates receptors of the innate immune system in CD4+ T cells. A surprising discovery in this project was that HIV activates “pattern-recognition receptors” TLR7, 8 and 9 upon uptake in T cells. We found that activation of TLR8 in T cells triggers inflammatory cytokine production and HIV replication. By using HIV patient samples from St. Olavs Hospital, we could demonstrate that TLR8 stimulation of T cells can re-activate latent HIV infection in patients treated by anti-retroviral therapy. This finding represents a previously unknown mechanism by which CD4+ T cells may detect HIV infection and can have the potential to develop new HIV treatment strategies. A manuscript with first authorship from this project has been written and will be submitted to a high impact journal.
Development of a novel cancer peptide vaccination method In collaboration with PCI Biotech (Oslo), we could show that the principle of photochemical internalization (PCI) provides a novel vaccination technology to effectively induce cancer-specific cytotoxic T cell responses. Our findings indicate that this method has the potential to improve efficacy of therapeutic cancer peptide vaccination.
Findings from this research project will be followed up in a new 5-year project funded by Samarbeidsorganet HMN-NTNU (90176000) with focus on continuation of the HIV work.
In addition, results from the project could show that PCI peptide vaccination has great potential as novel strategy to realize therapeutic cancer vaccination with peptides derived from the patients’ cancer cells. This method is minimally invasive, well-tolerated and approved for human use. Pre-clinical and clinical phase I cancer peptide vaccination trials with this method are planned.
High impact journal som det refereres til over?
Og fra 2017-2018 ved sluttrapporten står det at funn fra forskningen skal bli fulgt opp i et nytt 5 årig prosjekt som er finansiert med fokus HIV! Det nye prosjektet avsluttes i så fall i 2022-23. Mulig det rapporteres resultater underveis?
