A method for manufacturing T cells for use in a therapeutic cell composition, wherein the T cells express a T cell receptor (TCR) that recognizes an antigen on the surface of a target cell, the method comprising: a. processing a biological sample containing a population of T lymphocyte cells obtained from a donor subject that has a tumor to produce a first population of T lymphocyte cells; b. stimulating the first population with one or more first T-cell stimulating agents of lymphocytes under conditions for expansion of T cells in the population to produce a second population of activated T cells wherein the stimulation is performed in a closed system using serum free medium, wherein the one or more first T-cell stimulating agents is or comprises recombinant IL-2; c. co-culturing the second population of T cells in the presence of antigen presenting cells that present one or more non-native peptide on a major histocompatibility complex (MHC) in a closed system using serum free medium, said one or more non-native peptides are peptides corresponding to nonsynonymous somatic mutations associated in the tumor of the subject, to produce a third population of cells containing T cells comprising endogenous T cell receptors reactive to mutation encoding peptides of the tumor; d. selecting, from the third population of cells, the population of T cells containing endogenous TCR that are reactive to peptides present on the APCs based on one or more upregulation markers expressed on reactive or activated T cells in a closed system to produce a fourth population containing the selected T cells; and e. expanding the fourth population of selected cells in the presence of one or more second T-cell stimulating agents of lymphocytes under conditions to expand T cells in the population in a closed system using serum free medium to produce a composition of expanded T cells for use as a therapeutic cell composition, wherein the one or more second T-cell stimulating agents is or comprises recombinant IL-2. a. processing a biological sample containing a population of T lymphocyte cells obtained from a donor subject that has a tumor to produce a first population of T lymphocyte cells; b. stimulating the first population with one or more first T-cell stimulating agents of lymphocytes under conditions for expansion of T cells in the population to produce a second population of activated T cells wherein the stimulation is performed in a closed system using serum free medium, wherein the one or more first T-cell stimulating agents is or comprises recombinant IL-2; c. co-culturing the second population of T cells in the presence of antigen presenting cells that present one or more non-native peptide on a major histocompatibility complex (MHC) in a closed system using serum free medium, said one or more non-native peptides are peptides corresponding to nonsynonymous somatic mutations associated in the tumor of the subject, to produce a third population of cells containing T cells comprising endogenous T cell receptors reactive to mutation encoding peptides of the tumor; d. selecting, from the third population of cells, the population of T cells containing endogenous TCR that are reactive to peptides present on the APCs based on one or more upregulation markers expressed on reactive or activated T cells in a closed system to produce a fourth population containing the selected T cells; and e. expanding the fourth population of selected cells in the presence of one or more second T-cell stimulating agents of lymphocytes under conditions to expand T cells in the population in a closed system using serum free medium to produce a composition of expanded T cells for use as a therapeutic cell composition, wherein the one or more second T-cell stimulating agents is or comprises recombinant IL-2. <EOS>