Neo-epitope specific CD4+ T cells – Anti-tumoral mechanisms and their modulation

Abstract:

Cancer mutations have moved into the spotlight as targets for immunotherapy. We have recently found that the majority of the immunogenic mutations are recognized by CD4+ T cells. The project aims at gaining a better understanding of the immunobiology and anti-tumoral activity of neo-epitope specific CD4+ T cells (neo-CD4). Utilizing adoptively transferred CD4+ T cells transduced with neo-antigen specific TCR will allow us to study functional characteristics of neo-CD4+ T cells in tumor bearing mice and their mechanisms of tumor control. In a complementary manner, modulation of neo-CD4 T cell activity will be pursued using either tools available targeting the T cells directly or the suppressive tumor microenvironment.

Principal investigators:

Dr. med. Sebastian Kreiter
TRON – Translationale Onkologie an der Universitätsmedizin Mainz gGmbH
Freiligrathstraße 12, 55131 Mainz
Phone: +49 (0)6131 2161 480
E-Mail: sebastian.kreiter@tron-mainz.de
Web: http://biontech.de/de/ueber-biontech/management-team/sebastian-kreiter-m-d/ https://www.researchgate.net/profile/Sebastian_Kreiter

Univ.-Prof. Dr. med. Ugur Sahin
TRON – Translationale Onkologie an der Universitätsmedizin Mainz gGmbH
Freiligrathstraße 12, 55131 Mainz
Phone: +49 (0)6131 2161 201
E-Mail: sahin@uni-mainz.de
Web: http://tron-mainz.de/de/ueber-tron/management/
https://www.researchgate.net/profile/Ugur_Sahin2

Postdoc:

Dr. Thomas Bukur

Dr. Mathias Vormehr

Doctoral candidate:

Ikra Gizem Yildiz

Project-related publications:

Kreiter S, Vormehr M, van de Roemer N, Diken M, Löwer M, Diekmann J, Boegel S, Schrörs B, Vascotto F, Castle JC, Tadmor AD, Schoenberger SP, Huber C, Türeci Ö, Sahin U (2015) Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature 520: 692–696

Simon P, Omokoko TA, Breitkreuz A, Hebich L, Kreiter S, Attig S, Konur A, Britten CM, Paret C, Dhaene K, Dhaene K, Türeci Ö, Sahin U. Functional TCR retrieval from single antigen-specific human T cells reveals multiple novel epitopes. Cancer Immunol Res 2(12):1230-44

Castle JC, Loewer M, Boegel S, Tadmor AD, Boisguerin V, de Graaf J, Paret C, Diken M, Kreiter S, Türeci Ö, Sahin U (2014) Mutated tumor alleles are expressed according to their DNA frequency. Sci Rep 4:4743

Castle JC, Loewer M, Boegel S, de Graaf J, Bender C, Tadmor AD, Boisguerin V, Bukur T, Sorn P, Paret C, Diken M, Kreiter S, Türeci Ö, Sahin U. (2014) Immunomic, genomic and transcriptomic characterization of CT26 colorectal carcinoma. BMC Genomics 15:190

Castle JC, Kreiter S, Diekmann J, Löwer M, van de Roemer N, de Graaf J, Selmi A, Diken M, Boegel S, Paret C, Koslowski M, Kuhn AN, Britten CM, Huber C, Türeci O, Sahin U (2012) Exploiting the mutanome for tumor vaccination. Cancer Res 72(5):1081-91

Diken M, Kreiter S, Selmi A, Britten CM, Huber C, Türeci Ö, Sahin U (2011) Selective uptake of naked vaccine RNA by dendritic cells is driven by macropinocytosis and abrogated upon DC maturation. Gene Ther. 18(7):702-8

Kreiter S, Selmi A, Diken M, Koslowski M, Britten CM, Huber C, Türeci O, Sahin U (2010) Intranodal vaccination with naked antigen-encoding RNA elicits potent prophylactic and therapeutic antitumoral immunity. Cancer Res 70(22):9031-40

Kreiter S, Selmi A, Diken M, Sebastian M, Osterloh P, Schild H, Huber C, Türeci O, Sahin U (2008) Increased antigen presentation efficiency by coupling antigens to MHC class I trafficking signals. J Immunol 180(1):309-18

Kreiter S, Konrad T, Sester M, Huber C, Türeci O, Sahin U (2007) Simultaneous ex vivo quantification of antigen-specific CD4+ and CD8+ T cell responses using in vitro transcribed RNA. Cancer Immunol Immunother 56(10):1577-87