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We present a potent therapy, PEI-PEG-DUPA\/polyinosinic\/polycytosinic acid (PPD\/polyIC), which is targeted against PSMA. This treatment leads to tumor cell death and to the recruitment of immune cells, which attack neighboring tumor cells, even those that do not overexpress PSMA. In a mouse model, PPD\/polyIC led to shrinkage of all PSMA-overexpressing tumors and to complete regression in half of the animals. The multipronged approach invokes antitumor immunity, and reduces the probability of acquired resistance and disease recurrence. 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