title: 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.
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.
authors: The Department of Human Oncology, University of Wisconsin, Madison, WI 53705, USA.
authors: Richard K
authors: RK
authors: Yang
authors: Nicholas A
authors: NA
authors: Kalogriopoulos
authors: Alexander L
authors: AL
authors: Rakhmilevich
authors: Erik A
authors: EA
authors: Ranheim
authors: Songwon
authors: S
authors: Seo
authors: Kyungmann
authors: K
authors: Kim
authors: Kory L
authors: KL
authors: Alderson
authors: Jacek
authors: J
authors: Gan
authors: Ralph A
authors: RA
authors: Reisfeld
authors: Stephen D
authors: SD
authors: Gillies
authors: Jacquelyn A
authors: JA
authors: Hank
authors: Paul M
authors: PM
authors: Sondel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology / Q000378:metabolism; D009447:Neuroblastoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D007376:Interleukin-2; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011994:Recombinant Proteins; C493743:lorukafusp alfa
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