Methods of isolating T cells having antigenic specificity for a cancer-specific mutation

A method of preparing a pharmaceutical composition comprising T cells having antigenic specificity for a mutated amino acid sequence encoded by a cancer-specific mutation, the method comprising:

• identifying one or more genes in the nucleic acid of tumor cells of a patient, each gene containing a cancer-specific mutation that encodes a mutated amino acid sequence;
• inducing autologous antigen presenting cells (APCs) of the patient to present the mutated amino acid sequence encoded by each of the one or more identified genes;
• co-culturing autologous T cells of the patient with the autologous APCs that present the mutated amino acid sequence in one or more co-cultures;
• assessing each co-culture for autologous T cells having antigenic specificity for the mutated amino acid sequence presented in the context of an MHC class I molecule of the patient;
• assessing each co-culture for autologous T cells having antigenic specificity for the mutated amino acid sequence presented in the context of an MHC class II molecule of the patient;
• selecting the autologous T cells having antigenic specificity for a mutated amino acid sequence presented in the context of major histocompatibility complex (MHC) molecule(s) expressed by the patient;
• and
• combining the selected autologous T cells with a pharmaceutically acceptable carrier, thereby providing the pharmaceutical composition.