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

A method of isolating T cells having antigenic specificity for mutated amino acid sequences encoded by cancer-specific mutations, the method comprising:

• identifying more than one gene in the nucleic acid of tumor cells of a patient, each gene containing one of a cancer-specific mutation that encodes a mutated amino acid sequence;
• separately inducing autologous antigen presenting cells (APCs) of the patient to present the mutated amino acid sequence for each of the more than one identified genes;
• obtaining separate cultures of autologous T cells from multiple fragments of the patient's tumor;
• separately co-culturing each of the APCs presenting a mutated amino acid sequence with each of the separate cultures of autologous T cells
• 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
• isolating the selected autologous T cells.