The present invention relates to the discovery of novel methods of inducing a natural killer (NK) cell-mediated immune response and increasing NK activity in a mammal for the treatment of tumors and virus infections. The method comprises the steps of isolating peripheral blood mononuclear cells (PBMCs) from the subject, exposing the PBMCs in vitro to protein conjugate comprising granulocyte macrophage colony stimulating factor (GM-CSF) covalently linked to a soluble peptide antigen, under conditions effective to activate the PBMCs, and administering the activated PBMCs to the subject. The invention also relates to a method of detecting in a subject a cytotoxic NK cell-meditated immune response or NK cell activity in vitro by CD336 expression and/or lysis of the K562 tumor line. The invention further relates to a method for determining whether a subject has had a therapeutically effective response to a protein conjugate by assessing the NK activity of activated PBMCs from the subject.