Tolerogenic synthetic nanocarriers to reduce immune responses to therapeutic proteins

A composition comprising:

• (i) a first population of polymeric synthetic nanocarriers that are coupled to rapamycin, and
• (ii) a second population of polymeric synthetic nanocarriers that are coupled to therapeutic protein antigen-presenting cell (APC) presentable antigens,
• wherein the load of the rapamycin on average across the first population of polymeric synthetic nanocarriers is at least 2% but no more than 25% (weight/weight),
• wherein the load of the therapeutic protein APC presentable antigens on average across the second population of polymeric synthetic nanocarriers is between 1% and 10% weight/weight,
• wherein at least 75% of the polymeric synthetic nanocarriers of the first population of synthetic nanocarriers have a minimum dimension, obtained using dynamic light scattering, that is 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 composition is in an amount effective to reduce the generation of an undesired immune response against the therapeutic protein APC presentable antigens.