There was a non-significant trend towards dose-dependent tumor uptake, with higher uptake at doses ≥20 mg. Biodistribution was dose- and CEA-independent with major accumulation in lymphoid tissue compatible with IL-2R binding.
Blocking of IL-2 and IL-15 signaling by sγc attenuates the capacity of CD8<sup>+</sup> T cells to mount an optimal response to the tumor, with both quantitative and qualitative effects on antigen-specific CD8<sup>+</sup> T cells.
Compared with the vaccine group, immunization with tumor lysate in combination with propranolol significantly increased IL-2, IL-4, IL-12, IL-17, and IFN-γ cytokines.
Monoclonal antibodies directed against TNF-α, VEGF, and IL-6 has shown promising results to ameliorate inflammation and cancer, while direct administration of IL-2 has been shown to cause tumor regression.
However, when the product was administered together with L19-IL2 (a clinical-stage fusion protein capable of delivering IL2 to the tumor neovasculature), all treated mice in the combination group could be rendered tumor free, in a process that favored the influx of natural killer cells into the tumor mass.
We set out to develop a mathematical model to predict intratumoral CEA-IL2v concentrations following various systemic dosing intensities.<b>Experimental Design:</b> Sequential measurements of CEA-IL2v plasma concentrations in 74 patients with solid tumors were applied in a series of differential equations to devise a model that also incorporates the peripheral concentrations of IL2 receptor-positive cell populations (i.e., CD8<sup>+</sup>, CD4<sup>+</sup>, NK, and B cells), which affect tumor bioavailability of CEA-IL2v.
Therefore, the immunocorrective potentials of modified IL-2 and the anti-diabetic drug metformin are thoroughly discussed in the context of tumor immunobiology, mTOR pathways and revised Warburg effect.
Drug induced VKH syndrome has been reported in advanced melanoma patients receiving immunotherapy, including ipilimumab and adoptive cell transfer of Tumor-Infiltrating Lymphocyte associated with IL-2.
<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.
PTX and IL-2 co-loaded TSNs exhibited significant inhibition on tumor growth and metastasis, and prolonged overall survival for tumor-bearing mice compared with the corresponding monotherapies.
HddSBL reduced the tumor secreted serum rat IL-2 level upregulated by oncoVV, promoted viral replication, as well as inhibited the expression of antiviral factors in C6 glioblastoma cell line.
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.
The results demonstrated that IL‑2 and rAd‑p53 not only stimulated tumor‑specific cytotoxic T‑lymphocyte responses and increased regulatory CD4+ and cytotoxic CD8+ T cell proliferation, however additionally increased expression of apoptosis‑associated genes.
These results point toward the possibility of a negative impact of IL-2 in tumor immune responses, which may influence future immunotherapy treatments in CRC patients.
Gene set enrichment analysis was conducted to study the relevant mechanisms.Bladder cancer patients in COL5A2 low expression group were associated with better invasiveness (P < .0001), tumor grade (P = .001), T staging (P < .0001), N staging (P = .002), cancer specific survival (P < .0001), overall survival (P < .0001), and a trend of better M staging (P = .053) than those in COL5A2 high expression group.COL5A2 might affect the progression of bladder cancer through "Coagulation," "Hypoxia," "Apical junction," "Ultraviolet response," "Epithelial mesenchymal transition," "Angiogenesis," "KRAS (KRAS proto-oncogene, GTPase) signaling,"Complement,"IL2-STAT5-signaling," "Inflammatory response," "IL6-JAK-STAT3-signaling," "Myogenesis," "TNF α signaling," "Apoptosis," and "Hedgehog-signaling.
Viral expression of IL2 and TNFa altered the cytokine balance in the tumor microenvironment towards Th1 and increased the intratumoral proportion of CD8+ and conventional CD4+ T cells.
The results shown that combined SEP and αPD-L1 presented significant synergistic antitumor effects, increased the frequency of CD8<sup>+</sup> and CD4<sup>+</sup> T cells in spleen and tumor, cytotoxic activity of CTL in spleen, and IL-2 and IFN-γ levels in splenocytes and tumor.
An IL-2 construct combining a glycosylphosphatidylinositol (GPI) anchor with a rigid peptide linker leads to functional IL-2 expression on the tumour cell surface and in the tumour microenvironment.
Furthermore, Se-GP11 could enhance the immune functions during the tumor inhibition process of 5-Fu for increasing the cytokines secretion (IL-2 and TNF-α) and immune organs weights.