CPC A61K 35/17 (2013.01) [A61K 9/0019 (2013.01); A61K 9/0021 (2013.01); A61K 39/0008 (2013.01); A61K 39/0011 (2013.01); A61K 39/12 (2013.01); A61K 39/245 (2013.01); A61K 39/292 (2013.01); C12N 5/0636 (2013.01); C12N 7/00 (2013.01); A61K 2035/124 (2013.01); A61K 2039/5158 (2013.01); A61K 2039/53 (2013.01); A61K 2039/55566 (2013.01); A61K 2039/585 (2013.01); C12N 2501/2302 (2013.01); C12N 2501/2304 (2013.01); C12N 2501/2306 (2013.01); C12N 2501/2307 (2013.01); C12N 2501/2312 (2013.01); C12N 2501/2315 (2013.01); C12N 2501/2321 (2013.01); C12N 2501/999 (2013.01); C12N 2710/16034 (2013.01); C12N 2710/16234 (2013.01); C12N 2730/10134 (2013.01); C12N 2730/10171 (2013.01)] | 12 Claims |
1. A method for making a T cell population for use in altering the immunodominance hierarchy of a patient, comprising the steps of:
a. identifying at least one subdominant antigen or subdominant epitope in a sample obtained from the patient whose immunodominance hierarchy is to be altered, wherein the at least one subdominant antigen or subdominant epitope evokes a weaker tolerance or immune response than that of a dominant antigen or dominant epitope;
b. obtaining one or more samples from the patient, wherein the one or more samples comprise antigen presenting cells (APCs) and peripheral blood mononuclear cells (PBMCs);
c. exposing the APCs to a peptide mix derived from one or more subdominant antigens or epitopes;
d. cultivating from the PBMCs a T cell population comprising T cells capable of recognizing said subdominant antigen or epitope by
(i) exposing the PBMCs to the APCs from step (c) in media comprising a cytokine mix consisting of IL-7 and IL-15, and lacking IL-12;
(ii) expanding the T cells in media lacking IL-6, IL-12, and IL-27, and
(iii) optionally restimulating the T cells by exposing to the APCs from step (c).
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