Combination of immune effector cells specific for a target antigen and hematopoietic calls that express the target antigen in an altered form

A method for immunotherapy of a patient to remove target cells therefrom, the method comprising:

• (a) obtaining a population of immune effector cells,
• wherein the immune effector cells are derived from cells of the patient or an allogeneic effector cell donor and modified to express a chimeric recombinant antigen-recognizing receptor (CAR) that binds an extracellular epitope of a target antigen,
• wherein the target antigen is a cell surface antigen expressed on said target cells and on cells of a non-target hematopoietic cell subpopulation of the patient;
• (b) obtaining cells of the non-target hematopoietic cell subpopulation from the patient or an allogeneic cell donor;
• (c) producing a progeny cell population from the non-target hematopoietic cell subpopulation by a process that comprises gene-editing the cells obtained in step (b) and obtaining progeny of the gene-edited cells, wherein said gene-editing results in expression of an altered form of the target antigen by cells of the progeny cell population,
• wherein the altered form of the target antigen has at least one amino acid substitution or deletion in the extracellular epitope bound by the CAR, wherein the CAR has lower binding affinity to the altered form of the target antigen compared with the target antigen;
• (d) administering the immune effector cells and cells of the progeny cell population to the patient.