Immunotherapy to enhance the response of T cells to tumor cells by inhibiting expression of the Notch ligand

Described is the use of a T cell having enhanced reactivity towards a tumor cell for the preparation of a medicament for the therapeutic and/or prophylactic treatment of a malignancy. The T cell is prepared by exposing a T cell obtained from a patient to an agent which is capable of reducing or preventing expression or interaction of an endogenous Notch or Notch ligand in the cell. The T cell comprises a T cell receptor specific for a tumour antigen expressed by the tumour cell. The T cell can also be prepared by exposing an antigen presenting cell (APC) obtained from a tumour to an agent which is capable of reducing or preventing expression or interaction of an endogenous Notch or Notch ligand in the T cell when the T cell is contacted with the APC or by exposing a tumour cell obtained from a patient with to an agent which is capable of reducing or preventing expression or interaction of an endogenous Notch or Notch ligand in the T cell when the T cell is contacted with the tumour cell. Also described is an anti-tumor vaccine comprising a tumour antigen and an agent which is capable of reducing or preventing interaction, expressing or processing of Notch or a Notch ligand.