Seminar: Ugur Sahin

Individually tailored cancer immunotherapies

17 February 2016 12:00 hrs. - 13:00 hrs.
Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route 289
Individually tailored cancer immunotherapies

Ugur Sahin, Translationale Onkologie an der Universitätsmedizin der 
Johannes Gutenberg-Universität Mainz GmbH, Germany


Carl Figdor, Dept. of Tumor Immunology, RIMLS

17-02-2016 12:00:0017-02-2016 13:00:00Europe/AmsterdamIndividually tailored cancer immunotherapies Figdor Lecture Theatre, 8th floor RIMLS Building, Geert Grooteplein 26-28, route

Remarks / more information:

undefinedRNA vaccines offer the opportunity to delivery a wide range of tumor antigens enabling individualized tailored immunotherapies.  Testing carriers for delivery of antigen-encoding RNA vaccines into DC, we discovered a nanoparticulate RNA-lipoplex (RNA-LPX) which when administered intravenously targets DC with high selectivity. The lipoplex protects RNA from extracellular ribonucleases and mediates efficient uptake and expression of the encoded antigen by DC populations and macrophages (MΦ) in the spleen, lymph nodes and the bone marrow. RNA-LPX vaccines trigger TLR7-stimulated Interferon-α (IFNα) release from plasmacytoid DC (pDC) and MΦ. Thereby they drive maturation of DC in situ and initiate inflammatory immune mechanisms reminiscent of those in the early systemic phase of viral infection. RNA-LPX encoded vaccine enables induction of powerful immune responses against different target types such as viral oncogenes, mutant neo-epitopes and endogenous tumor antigens, resulting in rejection of advanced progressive tumors in an IFNα-dependent fashion, as well as memory T cells protecting from re-challenge. Data from the first melanoma patient treated in an ongoing phase I dose escalation trial with GMP-manufactured RNA-LPX encoding shared tumor antigens demonstrate swift clinical translation and feasibility of this concept. The induction of IFNα and of a strong antigen-specific T cell response in this patient treated at the lowest dose level supports the experimentally determined mode of action and exemplifies the outstanding potency of RNA-LPX vaccines. As virtually any polypeptide-based antigen can be encoded as RNA vaccine3,4,5, our data establishes RNA-LPX as universally applicable novel vaccine class for intravenous DC targeting and synchronized induction of both highly potent adaptive as well as type I interferon-mediated innate immune mechanisms for cancer immunotherapy.

Key publications:

  • Retrieval of functional TCRs from single antigen-specific T cells: Toward individualized TCR-engineered therapies. Oncoimmunology 4: e1005523-e, 2015
  • Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature 520: 692-6, 2015
  • mRNA-based therapeutics - developing a new class of drugs. Nat Rev Drug Discov 13: 759-80, 2014

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