Intratumoral treatment of smaller mouse neuroblastoma tumors with a recombinant protein consisting of IL-2 linked to the hu14.18 antibody increases intratumoral CD8+ T and NK cells and improves survival
Richard K Yang, Nicholas A Kalogriopoulos, Alexander L Rakhmilevich, Erik A Ranheim, Songwon Seo, Kyungmann Kim, Kory L Alderson, Jacek Gan, Ralph A Reisfeld, Stephen D Gillies, Jacquelyn A Hank, Paul M Sondel, Richard K Yang, Nicholas A Kalogriopoulos, Alexander L Rakhmilevich, Erik A Ranheim, Songwon Seo, Kyungmann Kim, Kory L Alderson, Jacek Gan, Ralph A Reisfeld, Stephen D Gillies, Jacquelyn A Hank, Paul M Sondel
Abstract
Hu14.18-IL2 is an immunocytokine (IC) consisting of human IL-2 linked to hu14.18 mAb, which recognizes GD2 disialoganglioside. Phase II clinical trials of intravenous-hu14.18-IL2 (IV-IC) in neuroblastoma and melanoma are underway, and have already demonstrated activity in neuroblastoma. In our Phase II trial, lower neuroblastoma burden at the time of treatment was associated with a greater likelihood of clinical response to IV-IC. We have previously shown that intratumoral-hu14.18-IL2 (IT-IC) compared to IV-IC results in enhanced local and systemic antitumor activity in tumor-bearing mice. We utilized a mouse model to investigate the impact of tumor burden on hu14.18-IL2 treatment efficacy in IV- versus IT-treated animals. Studies presented here describe the analyses of tumor burden at the initiation of treatment and its effects on treatment efficacy, survival, and tumor-infiltrating leukocytes in A/J mice bearing subcutaneous NXS2 neuroblastoma. We show that smaller tumor burden at treatment initiation is associated with increased infiltration of NK and CD8+ T cells and increased overall survival. NXS2 tumor shrinkage shortly after completion of the 3 days of hu14.18-IL2 treatment is necessary for long-term survival. This model demonstrates that tumor size is a strong predictor of hu14.18-IL2-induced lymphocyte infiltration and treatment outcome.
Conflict of interest statement
Conflict of Interest:
The authors declare that they have no conflict of interest.
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Source: PubMed