Tolerogenic synthetic nanocarriers for antigen-specific deletion of T effector cells

A method comprising:

• (A) administering to a subject according to a protocol that was previously shown to reduce the number or activity of antigen-specific T effector cells in one or more test subjects:
• (i) a population of polymeric synthetic nanocarriers coupled to rapamycin, and
• (ii) MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen that are not coupled to any synthetic nanocarriers;
• or
• (B) reducing the number or activity of antigen-specific T effector cells in one or more test subjects by administering to the one or more test subjects:
• (i) a population of polymeric synthetic nanocarriers coupled to rapamycin, and
• (ii) MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen that are not coupled to any synthetic nanocarriers;
• or
• (C) administering to a subject:
• (i) a population of polymeric synthetic nanocarriers coupled to rapamycin, and
• (ii) MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen that are not coupled to any synthetic nanocarriers;
• wherein the population of synthetic nanocarriers and MHC Class I-restricted and/or MHC Class II-restricted epitopes of an antigen are in an amount effective to reduce the number or activity of antigen-specific T effector cells,
• wherein at least 75% of the synthetic nanocarriers of the population of 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, and
• wherein the load of the rapamycin on average across the population of synthetic nanocarriers is at least 2% but no more than 25% (weight/weight).