2020

Reinhard K, Rengstl B, Oehm P, Michel K, Billmeier A, Hayduk N, Klein O, Kuna K, Ouchan Y, Wöll S, Christ E, Weber D, Suchan M, Bukur T, Birtel M, Jahndel V, Mroz K, Hobohm K, Kranz L, Diken M, Kühlcke K, Türeci Ö, Sahin U. (2020) An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors. Science. pii: eaay5967. 

DOI, PMID

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Chimeric antigen receptor (CAR)-T cells have shown efficacy in patients with B cell malignancies. Yet their application for solid tumors has challenges that include limited cancer-specific targets and non-persistence of adoptively transferred CAR-T cells. Here we introduce the developmentally regulated tight junction protein claudin 6 (CLDN6) as a CAR target in solid tumors, and a strategy to overcome inefficient CAR-T cell stimulation in vivo. We demonstrate that a nanoparticulate RNA vaccine, designed for body-wide delivery of the CAR antigen into lymphoid compartments, stimulates adoptively transferred CAR-T cells. Presentation of the natively folded target on resident dendritic cells promotes cognate and selective expansion of CAR-T cells. Improved engraftment of CAR-T cells and regression of large tumors in difficult-to-treat mouse models was achieved at sub-therapeutic CAR-T cell doses.

 

Vormehr M, Diken M, Türeci Ö, Sahin U, Kreiter S. (2020) Personalized Neo-Epitope Vaccines for Cancer Treatment. In: Theobald M. (eds) Current Immunotherapeutic Strategies in Cancer. Recent Results in Cancer Research, 214:153-167. Springer.  

DOI, PMID

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After more than a century of efforts to establish cancer immunotherapy in clinical practice, the advent of checkpoint inhibition (CPI) therapy was a critical breakthrough toward this direction (Hodi et al. in Cell Rep 13(2):412–424, 2010; Wolchok et al. in N Engl J Med 369(2):122–133, 2013; Herbst et al. in Nature 515(7528):563–567, 2014; Tumeh et al. in Nature 515(7528):568–571, 2014). Further, CPIs shifted the focus from long studied shared tumor-associated antigens to mutated ones. As cancer is caused by mutations in somatic cells, the concept to utilize these correlates of ‘foreignness’ to enable recognition and lysis of the cancer cell by T cell immunity seems an obvious thing to do.