Prolonged survival after intraperitoneal interleukin-2 immunotherapy for recurrent ovarian cancer

Minor, David R.; Moores, Samantha P.; Chan, John K.

doi:10.1016/j.gore.2017.09.009

Cited by 9 publications

(6 citation statements)

References 6 publications

(7 reference statements)

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“…A schematic diagram to summarize the effects of 46F2SIP/L19-IL2 combined therapy in SKOV3 human ovarian carcinoma model is reported in Figure 7. Previously, prolonged survival in a patient with recurrent ovarian cancer successfully treated with intra-peritoneal interleukin-2 was reported [50]. When administered locally in the tumor, IL-2 induces the release of pro-inflammatory mediators, increasing sensitivity to further immune attack.…”

Section: Discussionmentioning

confidence: 99%

L19-IL2 Immunocytokine in Combination with the Anti-Syndecan-1 46F2SIP Antibody Format: A New Targeted Treatment Approach in an Ovarian Carcinoma Model

Orecchia

Balza

Pietra

et al. 2019

Cancers

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Epithelial ovarian cancer (EOC) is the fifth most common cancer affecting the female population. At present, different targeted treatment approaches may improve currently employed therapies leading either to the delay of tumor recurrence or to disease stabilization. In this study we show that syndecan-1 (SDC1) and tumor angiogenic-associated B-fibronectin isoform (B-FN) are involved in EOC progression and we describe the prominent role of SDC1 in the vasculogenic mimicry (VM) process. We also investigate a possible employment of L19-IL2, an immunocytokine specific for B-FN, and anti-SDC1 46F2SIP (small immuno protein) antibody in combination therapy in a human ovarian carcinoma model. A tumor growth reduction of 78% was obtained in the 46F2SIP/L19-IL2-treated group compared to the control group. We observed that combined treatment was effective in modulation of epithelial-mesenchymal transition (EMT) markers, loss of stemness properties of tumor cells, and in alleviating hypoxia. These effects correlated with reduction of VM structures in tumors from treated mice. Interestingly, the improved pericyte coverage in vascular structures suggested that combined therapy could be efficacious in induction of vessel normalization. These data could pave the way for a possible use of L19-IL2 combined with 46F2SIP antibody as a novel therapeutic strategy in EOC.

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Section: Discussionmentioning

confidence: 99%

L19-IL2 Immunocytokine in Combination with the Anti-Syndecan-1 46F2SIP Antibody Format: A New Targeted Treatment Approach in an Ovarian Carcinoma Model

Orecchia

Balza

Pietra

et al. 2019

Cancers

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“…IL-2 causes activation, proliferation, and trafficking of T-cells and natural killer cells. When administered locally it may change a non-inflamed tumor into an inflamed tumor, perhaps thereby increasing sensitivity of that tumor to further immune attack [ 34 ]. One previous meta-analysis shows that IL-2 or induced killer cells combination therapy displays a considerable efficacy in treating NSCLC and thus improves overall survival.…”

Section: Discussionmentioning

confidence: 99%

Thoracic injection of low-dose interleukin-2 as an adjuvant therapy improves the control of the malignant pleural effusions: a systematic review and meta-analysis base on Chinese patients

Han¹,

Jiang²,

Yao³

et al. 2018

BMC Cancer

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BackgroundInterleukin-2 (IL-2) is an important immunotherapy cytokine for various diseases including cancer. Some studies reported the efficacy and safety on cisplatin combined with IL-2 versus cisplatin alone for treating malignant pleural effusion (MPE) through thoracic injection.MethodsWe searched these studies from medical electronic database. A total of 18 studies that met the inclusion criteria were recruited in this meta-analysis. Pooled odds ratios (OR) with 95% confidence intervals (CI) were determined by the fixed effects model of meta-analysis.ResultsThe objective response rate (ORR) and disease control rate (DCR) of cisplatin plus IL-2 for controlling MPE was significantly higher than that of cisplatin alone (p < 0.001). In addition, compared with cisplatin alone, the presence of IL-2 improved the quality of life (QOL) of patients with MPE (p < 0.001). Although the use of IL-2 seemed to increase the probability of fever in patients (p = 0.001), it did not lead to extra other side effects (AEs) including myelotoxicity, nausea/vomiting and chest pain (p > 0.05).ConclusionsThe low-dose IL-2 improved the ORR, DCR and QOL of patients in the treatment of MPE. Although it may cause fever in patients, it did not increase other AEs.

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“…The US FDA has approved the use of INF-γ and IL-2 as single agents for the clinical treatment of malignancies. Clinical trials of INF-γ and IL-2 therapies in solid malignancies, such as bladder carcinoma and ovarian cancer, have met with varying degrees of success (21,22). Several other cytokines, such as TNF-α, have been demonstrated to exhibit antitumor efficacy against cancer, for example sarcoma and breast cancer (23,24).…”

Section: Discussionmentioning

confidence: 99%

Toll‑like receptor agonist rMBP‑NAP enhances antitumor cytokines production and CTL activity of peripheral blood mononuclear cells from patients with lung cancer

Ding

Zhang

et al. 2018

Oncol Lett

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Toll-like receptor (TLR) agonists are known for their ability to inhibit tumor progression via enhancing antitumor cytokines production and cytotoxic T lymphocyte (CTL) activity. Recombinant Helicobacter pylori neutrophil-activating protein fused with maltose-binding protein (rMBP-NAP) has been reported as a novel TLR agonist for antitumor treatment in murine models. The present study aimed to determine the potential and efficacy of the rMBP-NAP for antitumor treatment prior to further clinical trials. The rMBP-NAP was expressed and purified for subsequent experiments. Peripheral blood mononuclear cells (PBMCs) from health donors and patients with lung cancer (LC) were incubated with PBS and 0.2 mg/ml rMBP-NAP. Antitumor cytokines production was assayed using ELISA and reverse transcription-quantitative polymerase chain reaction analysis. The cytolytic activity of PBMCs and the number of Interferon-γ (IFN-γ)-secreting cells were assayed using lactate dehydrogenase and Enzyme-linked ImmunoSpot assays, respectively. The results from the present study revealed that the expression of IFN-γ, interleukin (IL)-2, tumor necrosis factor-α and IL-12 of PBMCs from patients with LC and healthy donors were significantly increased following treatment with rMBP-NAP (P<0.05). Additionally, rMBP-NAP significantly upregulated the number of IFN-γ-secreting cells in PBMCs and prominently increased the cytotoxic activity of PBMCs (P<0.05). Furthermore, the expression of TLR2 was significantly enhanced following rMBP-NAP stimulation (P<0.05), which indicated that rMBP-NAP may serve an antitumor role via TLR2 signaling pathways. Overall, these results demonstrated that rMBP-NAP possesses the potential to be a novel immunomodulatory candidate drug and requires further evaluation in clinical trials.

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Prolonged survival after intraperitoneal interleukin-2 immunotherapy for recurrent ovarian cancer

Abstract: HighlightsA case report of a 14 year remission of recurrent ovarian cancer with intraperitoneal aldesleukin (IL-2) is presented.Intraperitoneal IL-2 was given with little toxicity.Immunotherapy may have the potential for durable remissions in ovarian cancer.

Cited by 9 publications

References 6 publications

L19-IL2 Immunocytokine in Combination with the Anti-Syndecan-1 46F2SIP Antibody Format: A New Targeted Treatment Approach in an Ovarian Carcinoma Model

L19-IL2 Immunocytokine in Combination with the Anti-Syndecan-1 46F2SIP Antibody Format: A New Targeted Treatment Approach in an Ovarian Carcinoma Model

Thoracic injection of low-dose interleukin-2 as an adjuvant therapy improves the control of the malignant pleural effusions: a systematic review and meta-analysis base on Chinese patients

Toll‑like receptor agonist rMBP‑NAP enhances antitumor cytokines production and CTL activity of peripheral blood mononuclear cells from patients with lung cancer

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