scholarly journals A folate receptor-targeted lipoplex delivering interleukin-15 gene for colon cancer immunotherapy

Oncotarget ◽  
2016 ◽  
Vol 7 (32) ◽  
pp. 52207-52217 ◽  
Author(s):  
Xiao Liang ◽  
Min Luo ◽  
Xia-Wei Wei ◽  
Cui-Cui Ma ◽  
Yu-Han Yang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Immunotherapy ◽  
Folate Receptor ◽  
Interleukin 15

scholarly journals A novel dual-prodrug carried by cyclodextrin inclusion complex for the targeting treatment of colon cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lin Chen ◽  
Yan Lin ◽  
Zijun Zhang ◽  
Ruisheng Yang ◽  
Xiaosheng Bai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ulcerative Colitis ◽  
Colon Cancer ◽  
Inclusion Complex ◽  
Tumor Suppression ◽  
Folate Receptor ◽  
Significant Inhibition ◽  
Aminosalicylic Acid ◽  
Anti Inflammatory

Abstract Background There is an obvious correlation between ulcerative colitis and colorectal cancer, and the risk of colorectal cancer in patients with ulcerative colitis is increasing. Therefore, the combination therapy of anti-inflammatory and anti-tumor drugs may show promising to inhibit colon cancer. 5-aminosalicylic acid (5-ASA) with anti-inflammatory function is effective for maintaining remission in patients with ulcerative colitis and may also reduce colorectal cancer risk. Histone deacetylase (HDAC) plays an essential role in the progression of colon cancer. Butyric acid (BA) is a kind of HDAC inhibitor and thus shows tumor suppression to colon cancer. However, the volatile and corrosive nature of BA presents challenges in practical application. In addition, its clinical application is limited due to its non-targeting ability and low bioavailability. We aimed to synthesize a novel dual-prodrug of 5-ASA and BA, referred as BBA, to synergistically inhibit colon cancer. Further, based on the fact that folate receptor (FR) is over-expressed in most solid tumors and it has been identified to be a cancer stem cell surface marker in colon cancer, we took folate as the targeting ligand and used carboxymethyl-β-cyclodextrin (CM-β-CD) to carry BBA and thus prepared a novel inclusion complex of BBA/FA-PEG-CM-β-CD. Results It was found that BBA/FA-PEG-CM-β-CD showed significant inhibition in cell proliferation against colon cancer cells SW620. It showed a pro-longed in vivo circulation and mainly accumulated in tumor tissue. More importantly, BBA/FA-PEG-CM-β-CD gave great tumor suppression effect against nude mice bearing SW620 xenografts. Conclusions Therefore, BBA/FA-PEG-CM-β-CD may have clinical potential in colon cancer therapy. Graphical Abstract

scholarly journals Effect of Toxoplasma gondii on colon cancer growth in mouse model

2021 ◽  
Vol 9 (2) ◽  
pp. 168-176
Author(s):  
Farideh Zavareh ◽  
◽  
Mahboubeh Hadiipour ◽  
Reza Kalantari ◽  
Somayeh Mousavi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Immune System ◽  
Toxoplasma Gondii ◽  
Tumor Growth ◽  
Cancer Immunotherapy ◽  
Target Therapy ◽  
Control Group ◽  
Neoplastic Cells ◽  
Tumor Environment ◽  
The Difference

Despite all advances in cancer treatment methods, failure of treatment is a major concern. This failure can be caused by tumor environment made by tumor cells and prevents immune system to reach neoplastic cells. So, cancer immunotherapy and target therapy are in the focus of scientists. Due to the inverse relationship shown between parasites and cancer, parasites are a candidate for use in cancer immunotherapy. Toxoplasma gondii is an intracellular parasite invades many cells of vertebrae spices but make symptoms only in fetus and immuno-deficient person. Studies have shown T. gondii can stimulate immune system against neoplastic cells and break fort of tumor environment. In this experimental work, Colon cancer bearing mice randomly divided into three groups. Groups 1 and 2 were injected with either lysate or irradiated tachyzoite of T. gondii respectively. The third group were left intact as control group. Our resulted data showed that in irradiated tachyzoite or lysate treated groups there was a significant reduction in tumor growth in comparison with control group. However, the difference in survival time was not statistically significant. In conclusion, treatment with T. gondii antigens resulted in suppression of tumor growth.

Blood Concentrations of Interleukin-15 in Cancer Patients and Their Variations during Interleukin-2 Immunotherapy: Preliminary Considerations

1998 ◽  
Vol 13 (3) ◽  
pp. 169-171 ◽  
Author(s):  
P. Lissoni ◽  
F. Rovelli ◽  
M. Mandalà ◽  
S. Barni
Keyword(s):  
Cancer Immunotherapy ◽  
Cancer Patients ◽  
Metastatic Cancer ◽  
Cell Cancer ◽  
Interleukin 2 ◽  
Serum Levels ◽  
Control Group ◽  
Blood Concentrations ◽  
Significant Difference ◽  
Interleukin 15

In addition to the better known cytokines IL-2 and IL-12, IL-15, which is mainly produced by macrophages, is a new antitumor cytokine with a mechanism of action similar to that of IL-2. At present, however, there are no data about IL-15 secretion in cancer patients. This study was carried out to evaluate IL-15 blood concentrations in patients with early or advanced cancer and their possible variations in response to IL-2 cancer immunotherapy. The study included 40 patients with solid tumors, 24 of whom had metastatic disease. In addition, IL-15 secretion was evaluated during subcutaneous low-dose IL-2 therapy (6 million IU/day for 6 days/week for 4 weeks) in 14 metastatic renal cell cancer patients by collecting blood samples at weekly intervals. The control group consisted of 40 age-matched healthy subjects. Serum levels of IL-15 were measured by an enzyme immunoassay. No significant difference in mean serum levels of IL-15 was observed between cancer patients and controls. Moreover, the mean serum levels of IL-15 found in metastatic cancer patients were not significantly different from those found in patients with limited disease. Finally, no significant changes in mean levels of IL-15 occurred during IL-2 cancer immunotherapy. This preliminary study would suggest that IL-15 secretion is substantially within the normal range in cancer patients, both in early and advanced disease, and no variation seems to occur in response to IL-2 administration.

Abstract 3863: Cancer immunotherapy: Could TK1 be used as a target for colon cancer

2016 ◽  
Author(s):  
Michelle H. Townsend ◽  
Evita G. Weagel ◽  
Wei Meng ◽  
Craig Chandler ◽  
Richard A. Robison ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Immunotherapy

scholarly journals Interleukin-15 dendritic cells as vaccine candidates for cancer immunotherapy

2013 ◽  
Vol 9 (9) ◽  
pp. 1956-1961 ◽  
Author(s):  
Sébastien Anguille ◽  
Eva Lion ◽  
Johan Van den Bergh ◽  
Heleen H Van Acker ◽  
Yannick Willemen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cancer Immunotherapy ◽  
Vaccine Candidates ◽  
Interleukin 15

scholarly journals Interleukin-15 combined with an anti-CD40 antibody provides enhanced therapeutic efficacy for murine models of colon cancer

2009 ◽  
Vol 106 (18) ◽  
pp. 7513-7518 ◽  
Author(s):  
M. Zhang ◽  
Z. Yao ◽  
S. Dubois ◽  
W. Ju ◽  
J. R. Muller ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Therapeutic Efficacy ◽  
Murine Models ◽  
Interleukin 15

scholarly journals Interleukin-15 in cancer immunotherapy: IL-15 receptor complex versus soluble IL-15 in a cancer cell-delivered murine leukemia model

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Alexandra Berger ◽  
Sarah J. Colpitts ◽  
Melanie S. S. Seabrook ◽  
Caren L. Furlonger ◽  
Maura B. Bendix ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Cancer Cell ◽  
Receptor Complex ◽  
Complex Versus ◽  
Interleukin 15 ◽  
Murine Leukemia

scholarly journals Preclinical Evaluation of Recombinant Human IL15 Protein Fused with Albumin Binding Domain on Anti-PD-L1 Immunotherapy Efficiency and Anti-Tumor Immunity in Colon Cancer and Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1789
Author(s):  
Fei-Ting Hsu ◽  
Yu-Chang Liu ◽  
Chang-Liang Tsai ◽  
Po-Fu Yueh ◽  
Chih-Hsien Chang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Half Life ◽  
Significant Proportion ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Binding Domain ◽  
Albumin Binding ◽  
Effector Cells ◽  
Interleukin 15 ◽  
Immunosuppressive Cells

Anti-PD-L1 antibody monotherapy shows limited efficacy in a significant proportion of the patients. A common explanation for the inefficacy is a lack of anti-tumor effector cells in the tumor microenvironment (TME). Recombinant human interleukin-15 (hIL15), a potent immune stimulant, has been investigated in clinical trial with encouraging results. However, hIL15 is constrained by the short half-life of hIL15 and a relatively unfavorable pharmacokinetics profile. We developed a recombinant fusion IL15 protein composed of human IL15 (hIL15) and albumin binding domain (hIL15-ABD) and explored the therapeutic efficacy and immune regulation of hIL-15, hIL15-ABD and/or combination with anti-PD-L1 on CT26 murine colon cancer (CC) and B16-F10 murine melanoma models. We demonstrated that hIL15-ABD has significant inhibitory effect on the CT26 and B16-F10 tumor growths as compared to hIL-15. hIL-15-ABD not only showed superior half-life and pharmacokinetics data than hIL-15, but also enhance anti-tumor efficacy of antibody against PD-L1 via suppressive effect on accumulation of Tregs and MDSCs and activation of NK and CD8+T cells. Immune suppressive factors including VEGF and IDO were also decreased by combination treatment. hIL15-ABD combined with anti-PD-L1 antibody increased the activity of anti-tumor effector cells involved in both innate and adaptive immunities, decreased the TME’s immunosuppressive cells, and showed greater anti-tumor effect than that of either monotherapy.

Sign in / Sign up

Export Citation Format

Share Document