Subject-specific tumor inhibiting cells and the use thereof

A method for producing Cbl-b−/− tumor inhibiting cells (TICs), the method comprising the steps of:

• a) inactivating genomic Cbl-b genes of immune cells to produce the Cbl-b−/− TICs, wherein the Cbl-b−/− TICs are free from Cbl-b bio-function and free from deoxyribonucleic acids exogenous to the immune cells and free from viral nucleic acids exogenous to the immune cells, wherein said immune cells are tumor infiltrating lymphocytes (TILs) from a tumor of a subject, a xenograft tumor derived from the tumor of said subject, or a combination thereof, and wherein said Cbl-b−/− TICs are specific to said tumor of said subject and have tumor specific cytotoxicity mediated via T cell receptor (TCR);
• b) optionally, propagating the Cbl-b−/− TICs in in vitro cell culture;
• and
• c) optionally, harvesting the Cbl-b−/− TICs from the in vitro cell culture.

A method for treating a tumorous condition of a subject in need thereof, the method comprising the steps of:

• a) inactivating genomic Cbl-b genes of immune cells of the subject to produce Cbl-b−/− tumor inhibiting cells (TICs), wherein the Cbl-b−/− TICs have inactivated Cbl-b gene alleles and are free from Cbl-b bio-function, and wherein the Cbl-b−/− TICs are free from deoxyribonucleic acids exogenous to the immune cells and free from viral nucleic acids exogenous to the immune cells, wherein said immune cells are tumor infiltrating lymphocytes (TILs) from a tumor of said subject, a xenograft tumor derived from the tumor of said subject, or a combination thereof, and wherein said Cbl-b−/− TICs are specific to said tumor of said subject and have tumor specific cytotoxicity mediated via T cell receptor (TCR);
• b) optionally, propagating the Cbl-b−/− TICs in in vitro cell culture;
• and
• c) administering the Cbl-b−/− TICs to the subject.