To investigate whether in vivo anti-cancer potential of HER2-specific CAR T cells utilizing 4-1BB or CD28 signaling differ, we treated SKOV3 tumor-bearing Rag−/− mice by a single intravenous injection of untransduced or HER2-specific SS-4-1BB/ζ, LS-4-1BB/ζ-, SS-28/ζ-, LS-28/ζ-CAR CD8+ T cells. Here, CD28 is linked to neoplasm.