Neoantigens and uses thereof

A method of treating cancer in a subject in need thereof, the method comprising:

• (a) administering to the subject a first pharmaceutical composition comprising autologous T cells, wherein the autologous T cells comprise:
• (i) a first plurality of autologous T cells stimulated with a first population of antigen presenting cells (APCs) having a first peptide comprising a first neoepitope of a region of a protein, wherein APCs of the first population of APCs present the first neoepitope as a complex with a class II HLA protein encoded by a class II HLA allele of the subject;
• and
• (b) subsequent to (a), administering to the subject a second pharmaceutical composition comprising autologous T cells, wherein the autologous T cells comprise both (i) and
• (ii) a second plurality of autologous T cells stimulated with a second population of APCs having a second peptide comprising a second neoepitope of the region of the same protein, wherein APCs of the second population of APCs present the second neoepitope as a complex with a class I HLA protein encoded by a class I HLA allele of the subject;
• wherein:
• (A) the first neoepitope and the second neoepitope comprise the same mutation,
• (B) the first peptide is different from the second peptide and the first peptide is at least one amino acid longer in length than the second peptide, and
• (C) the first neoepitope is longer than the second neoepitope, wherein the second neoepitope has a length of from 8 to 13 amino acids and the first neoepitope has a length of from 9 to 25 amino acids.