Cancer Immunology, Immunotherapy

, Volume 62, Issue 8, pp 1303–1313 | Cite as

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
Original Article

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.

Keywords

Hu14.18-IL2 Immunocytokine Tumor-infiltrating leukocytes NKG2D Neuroblastoma 

Supplementary material

262_2013_1430_MOESM1_ESM.pdf (260 kb)
Supplementary material 1 (PDF 260 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Richard K. Yang
    • 1
  • Nicholas A. Kalogriopoulos
    • 1
  • Alexander L. Rakhmilevich
    • 1
    • 5
  • Erik A. Ranheim
    • 2
    • 5
  • Songwon Seo
    • 3
  • KyungMann Kim
    • 3
    • 5
  • Kory L. Alderson
    • 1
  • Jacek Gan
    • 1
  • Ralph A. Reisfeld
    • 6
  • Stephen D. Gillies
    • 7
  • Jacquelyn A. Hank
    • 1
    • 5
  • Paul M. Sondel
    • 1
    • 4
    • 5
  1. 1.The Department of Human OncologyUniversity of WisconsinMadisonUSA
  2. 2.The Departments of Pathology and Laboratory MedicineUniversity of WisconsinMadisonUSA
  3. 3.The Departments of Biostatistics and Medical InformaticsUniversity of WisconsinMadisonUSA
  4. 4.The Department of PediatricsUniversity of WisconsinMadisonUSA
  5. 5.The Department of Carbone Cancer CenterUniversity of WisconsinMadisonUSA
  6. 6.The Department of ImmunologyThe Scripps Research InstituteLa JollaUSA
  7. 7.Provenance Biopharmaceuticals Corp.WalthamUSA

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