Tolerogenic synthetic nanocarriers for generating CD8+ regulatory T cells

A method comprising:

• (A) administering to a subject a composition that comprises:
• (i) a first population of polymeric synthetic nanocarriers coupled to rapamycin or an analog thereof, and
• (ii) MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen,
• wherein the composition is in an amount effective to generate antigen-specific CD8+ regulatory T cells in the subject;
• or
• (B) generating antigen-specific CD8+ regulatory T cells in a subject by administering a composition that comprises:
• (i) a first population of polymeric synthetic nanocarriers coupled to rapamycin or an analog thereof, and
• (ii) MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen;
• or
• (C) administering to a subject a composition according to a protocol that was previously shown to generate antigen-specific CD8+ regulatory T cells in one or more test subjects;
• wherein the composition comprises:
• (i) a first population of polymeric synthetic nanocarriers coupled to rapamycin or an analog thereof, and
• (ii) MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen;
• and wherein the load of the rapamycin or an analog thereof on average across the first population of polymeric synthetic nanocarriers is at least 2% but no more than 25% (weight/weight), and wherein at least 75% of the polymeric synthetic nanocarriers of the first population of polymeric synthetic nanocarriers have a minimum dimension, obtained using dynamic light scattering, that is greater than 110 nm and a maximum dimension, obtained using dynamic light scattering, that is equal to or less than 500 nm.