In cell culture, IL15-activated NK cells induced higher ADCC against two GD<sup>+</sup> neuroblastoma PDXs than did IL2-activated NK cells (<i>P</i> < 0.001).
The humanized anti-GD2 antibody conjugated to IL2 (hu14.18-IL2) has clinical activity in neuroblastoma and is more effective in neuroblastoma-bearing mice than antibody and cytokine given separately.
In conclusion, IL-2 is an important component of immunotherapy because it can improve the cytolytic function of NK cells against neuroblastoma cells and could lower the antibody dose required for efficacy, thereby reducing toxicity.
We generated a bicistronic retroviral vector encoding a GD2-specific CAR and the IL-7Rα subunit, expressed the genes in EBV-CTLs, and assessed their capacity to control tumor growth in the presence of Treg in vitro and in vivo when exposed to either interleukin-2 (IL-2) or IL-7 in a neuroblastoma xenograft.
Similarly, a recently developed NK cell expansion system employing IL-2 plus lethally irradiated K562 feeder cells constitutively expressing membrane-bound IL-21 (K562 clone 9.mbIL21) resulted in activated NK cells derived from normal healthy donors and neuroblastoma patients that also utilized TRAIL to supplement cytotoxicity.
NK cell cytotoxicity against K562 and neuroblastoma cells increased and significantly higher cytokine secretion (eg, interferon-gamma, tumor necrosis factor-beta, macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta) was observed after IL-2 stimulation compared with freshly isolated NK cells.
They each received up to 8 subcutaneous injections of a vaccine combining lymphotactin--and interleukin-2 (IL-2)--secreting autologous neuroblastoma cells in a dose-escalating scheme.
Here we have compared the antitumour effect of fibroblasts and tumour cells transfected ex vivo to coexpress interleukin-2 (IL-2) and IL-12 in a syngeneic mouse model of neuroblastoma.
Only mice bearing FKN- and IL-2-enriched neuroblastoma tumors exhibited a reduction in primary tumor growth and a complete eradication of experimental liver metastases.
In summary, we demonstrated for the first time that chemokine gene therapy is amplified by targeted IL-2 suggesting a combination of both strategies as an adjuvant therapy for neuroblastoma.
New approaches to treating neuroblastoma MRD that are in early clinical trials include the cytotoxic retinoid fenretinide and the hu14.18-IL2 immunocytokine.
They received up to 8 subcutaneous injections of a vaccine combining lymphotactin (Lptn)- and interleukin-2 (IL-2)-secreting allogeneic neuroblastoma cells in a dose-escalating scheme.
Seven days after IL-2 gene-transfected neuroblastoma cell injection, unmodified neuro-2a cells were s.c. injected into the contralateral site of A/J mice and tumor growth was measured weekly.
To investigate the relevance of these animal models to pediatric malignancy, we used autologous unirradiated tumor cells transduced with an adenovirus-IL-2 to immunize 10 children with advanced neuroblastoma.
We have evaluated the safety, immunostimulatory, and antitumor activity of an interleukin-2-secreting allogeneic neuroblastoma cell line in 12 children with relapsed stage IV neuroblastoma.
The combination of IL-2 gene transfection and the xenograft model in nude mice was chosen on the basis of the low or absent expression of HLA class I antigen in human NB tumors.
We have used an E1a,1b/E3 deletion mutant of adenovirus containing either the lacZ or the human interleukin-2 (IL-2) gene to transduce human neuroblastoma cells.
A total of 90 clones were subsequently raised from IL-2-expanded TIL from six NB patients; 87/90 clones were of T cell lineage with a CD4+ or CD8+ immunophenotype, whereas the 3 remaining clones were of NK cell origin.
Co-culture of IL-2 transduced cell lines with patient lymphocytes induced potent cytotoxic activity against both transduced and parental neuroblastoma cell lines.