Addition of systemic IL2 increases effectiveness of hu14.18-IL2 immunocytokine therapy against NXS2 murine neuroblastoma

Abstract Introduction: The hu14.18-IL2 immunocytokine (IC) links rhIL2 to humanized anti-GD2 monoclonal antibody hu14.18 and inhibits NXS2 tumor growth in A/J mice. This study combined systemic IL2 with hu14.18-IL2 therapy to increase antitumor effects. Methods: A/J mice with subcutaneous NXS2 tumors received rhIL2 (50,000 IU/d by continuous infusion pump) × 7 d, IC (5 micrograms/d × 5), IC (22 micrograms/d × 5), or combined rhIL2 and IC (5 micrograms/d). Mice were also depleted of NK or T cells during combined therapy. Proliferation assays of human and murine cells with high-affinity IL2Rs (T cells) or intermediate-affinity IL2Rs (NK cells) were performed. Results: The combination of systemic IL2 and IC therapy resulted in durable resolution of NXS2 tumors. This antitumor effect was greater than that achieved by either rhIL2 or IC alone (p = 0.026 and 0.007). The efficacy of the combined treatment was dependent on NK and T cells. Although IL2 in the form of an immunocytokine and rhIL2 induce similar proliferation of human NK and T cells, the immunocytokine is less potent than rhIL2 at stimulating murine NK and T cells (3 to 20-fold less, respectively). Conclusions: The combination of systemic IL2 and hu14.18-IL2 is more effective than either therapy alone in A/J mice bearing subcutaneous NXS2 tumors and involves both NK and T cells. This may be the result of NK cell activation and expansion prior to IC treatment and reflect the stronger IL2-mediated action of rhIL2 than IC on murine IL2R-bearing cells.