Hla-class ii artificial antigen presenting cells in cd4 + t cell-based immunotherapy

CD4 T cell help is essential to promote robust cytotoxic T cell responses and could be harnessed to improve outcomes of cancer immunotherapy. To induce CD4+ T cell responses, the inventors have developed artificial antigen presenting cells (AAPCs) that derived from a mouse fibroblast cell line genetically modified to express a single human leukocyte antigen class II molecule (HLA-DR), the human CD80 costimulation as well as CD54 and CD58 adhesion molecules and that constitutively express an antigen (Ag) in peptide or protein forms in different compartments involved in the major histocompatibility complex class II Ag presentation pathway. In particular, the inventors show that the AAPC expressing the Ag peptide in the endoplasmic reticulum (ER) or protein at the plasma membrane were more potent than Epstein-Barr virus (EBV)-transformed B cells to present epitopes to specific CD4+ T-cells. Interestingly, AAPC targeting the Ag peptide in the ER was more efficient than peptide-pulsed AAPC or autologous APC to amplify memory Ag-specific CD4+ T cells that harbor a Th1 profile and express granzyme B. So, the AAPC system is a reliable and standardized tool to generate a high number of Ag-specific CD4+ with effector functions useful for a cancer adoptive immunotherapy. Thus, the present inventions relate to - an artificial antigen presenting cell that constitutively expresses an antigen along with a HLA-class II molecule and uses thereof in particular for amplifying and/or activating a population of antigen-specific CD4+ T cells. - method of amplifying a population of antigen-specific memory CD4+ T cells using artificial presenting cells expressing HLA class II molecules. In particular, the present invention relate to a method of amplifying a population of antigen-specific memory CD4+ T cells comprising the steps of i) providing a population of artificial antigen presenting cells consisting host cells that are genetically modified to stably express at least one MHC class II molecule along with at least one accessory molecule ii) loading the population of artificial antigen presenting cells of step i) with an amount of at least one antigen of interest and iii) coculturing the suitable population of a T cells with the population of artificial antigen presenting cells of step ii).

Keywords: HLA-II APC, T-Cell Immunotherapy, Chronical Viral Infection, Cancer, AutoImmune Disease, Transplantation
Patent Application number: EP15 306 925.7
Inventors:
Olivier TOUTIRAIS Brigitte LE MAUFF QUESTER
Publications:
Front Immunol. 2019 May 17;10:1081. doi: 10.3389/fimmu.2019.01081. eCollection 2019. Immunol Cell Biol. 2016 Aug;94(7):662-72. doi: 10.1038/icb.2016.25. Epub 2016 Feb 29.

Reference:

BIO15322-R1

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Patent filling date: 2015-12-04

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