Three out of 14 PDS revealed high levels of CD8-positive tumor-infiltrating T-lymphocytes (TILs), also showing elevated levels of immune-related cytokines such as IL1A, IL2, as well as markers that were very recently linked to enhanced response of immunotherapy in malignant melanoma, including CD27, and CD40L.
Potentially, IL-2/IFN might represent a treatment option in patients with active melanoma after established initial treatment with checkpoint inhibitors and BRAF/MEK-targeted therapies.
Efficacy of Adoptive Therapy with Tumor-infiltrating Lymphocytes and Recombinant Interleukin-2 in Advanced Cutaneous Melanoma: A Systematic Review and Meta-analysis.
The controlled responsive delivery of IL-2/Fc enabled the safe administration of repeated doses of the stimulant cytokine with no overt toxicity and improved efficacy against melanoma metastases in a mice model.
Neo-2/15 has superior therapeutic activity to IL-2 in mouse models of melanoma and colon cancer, with reduced toxicity and undetectable immunogenicity.
While IL-2 targets anti-tumor cytotoxic lymphocytes (CTLs) for the treatment of patients with melanoma or renal cell carcinoma, IL-2 directed at regulatory T (Treg) cells could have potential therapeutic value in several immune-related diseases including chronic graft-versus-host disease (cGVHD), type 1 diabetes (T1D) and systemic lupus erythematosus (SLE).
In this manuscript, we analyze the recurrence-free survival, overall survival and toxicity profile of adjuvant treatment with interleukin-2 (IL-2) and 5-(3,3-dimethyle-1-triazeno) imidazole-4-carboxamide (DTIC) for resected high-risk melanoma patients.
NCI 8628: A randomized phase 2 study of ziv-aflibercept and high-dose interleukin 2 or high-dose interleukin 2 alone for inoperable stage III or IV melanoma.
In this study, we demonstrate in the aggressive B16F10 mouse melanoma model that concomitant application of the anti-TRP1 Ab (clone TA99) with TLR3-7/8 or -9 ligands, and IL-2 strongly enhanced tumor control in a therapeutic setting.
In vitro assays revealed rapid but transient melanoma inhibition with T<sub>eff</sub> and gradual but prolonged melanoma inhibition with T<sub>mem</sub>; the addition of T<sub>mem</sub> enhanced the ability of T<sub>eff</sub> to inhibit melanoma in a manner that could be reproduced using conditioned media from activated T<sub>mem</sub> and blocked by the addition of anti-IL-2 blocking antibody.
The effects of flavonoid treatment on melanoma sensitivity towards T cells were investigated using Jurkat cell killing, cytotoxicity, cell viability, and IL-2 secretion assays.
Immune cells responsive to TNF-α IL-2 were studied using an immunocompetent mouse melanoma model (B16.OVA) infused with ovalbumin-specific T (OT-I) cells.
Treatment options have expanded beyond high-dose interleukin 2 and adoptive T-cell therapy to include inhibitors of immune checkpoints programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and small molecular inhibitors of pathways activated in melanoma, in particular the mitogen-activated protein kinase (MAPK) pathway.
Compared with chemotherapy, biochemotherapy (in this case, chemotherapy combined with both interferon-alpha and interleukin-2) and BRAF inhibitors improved progression-free survival; BRAF inhibitors (for BRAF-mutated melanoma) and anti-PD1 monoclonal antibodies improved overall survival.
<i>In vivo</i> administration of IAP antagonists and α-GalCer resulted in increased IFNγ and IL-2 production from iNKT cells and decreased tumor burden in a mouse model of melanoma lung metastasis.
Ninety one patients receiving IL2 therapy for metastatic renal cell carcinoma and melanoma at Huntsman Cancer institute (HCI), Utah from May 2009 to October 2016 were retrospectively evaluated for rigor prophylaxis.
Similar to melanoma, renal cell carcinoma (RCC) has been historically considered as an immunogenic tumor, with interleukin 2 (IL-2) and interferon alpha (IFN-α) being the first approved treatments in the 1990s.
We evaluated the efficacy and safety of intratumorally administered IL-2-coding adenoviruses in combination with tumor-infiltrating lymphocyte therapy in syngeneic Syrian hamsters bearing HapT1 pancreatic tumors and with T cell receptor transgenic ACT in B16.OVA melanoma bearing C57BL/6 mice.