Abstract: Methods are disclosed for stimulating an immune response against a target antigen, such as one or more tumor associated antigens. In particular examples the method includes reducing the number of CD4+ T cells in a subject after the subject receives a first dose of an immunogenic composition that includes the target antigen (such as a cancer vaccine), wherein the subject has a tumor that expresses the target antigen. The subject is administered a second dose of the immunogenic composition, thereby stimulating an immune response against the target antigen. In some examples the method also includes administering to the subject peripheral blood mononuclear cells (PBMCs) (for example a population of PBMCs depleted of CD25 cells, CD81 cells, CD134+ cells, Areg+ cells, Ptgr3+ cells, or combinations thereof) prior to receiving the first dose of the immunogenic composition.