Antitumour activity of cationic‐liposome‐conjugated adenovirus containing the CCL19 [chemokine (C‐C motif) ligand 19] gene

Abstract

CCL19 [chemokine (C-C motif) ligand 19; also known as MIP-3beta (macrophage inflammatory protein-3beta) or ELC (Epstein-Barr-virus-induced molecule 1 ligand chemokine)], one of the immunostimulatory cytokines, chemoattracts both DCs (dendritic cells) and T-lymphocytes. Adenoviral vector is one of the most used gene delivery vectors for cancer therapy because of its high gene-transfection efficiency. However, its wider application is limited, owing to immune responses that reduce transgene expression and decrease the efficacy of repeated administration. We constructed the recombinant replication deficient adenoviral vectors containing the CCL19 gene (Ad-CCL19) and combined them with PEG-PE [poly(ethylene glycol)-phosphatidylethanolamine]-modified cationic liposomes (Ad-CCL19/PEG-PE) for immunotherapy against murine fibrosarcoma. Although there were hardly any therapeutic differences between Ad-CCL19- and Ad-CCL19/PEG-PE-treated mice that were observed at the second administration, the final results demonstrated that Ad-CCL19/PEG-PE-treated mice survived much longer. The antitumour efficacy may be related to the high level of CCL19 after the final administration and lasting expression of IFN-gamma (interferon-gamma) and IL-12 (interleukin-12) in the Ad-CCL19/PEG-PE-treated group, which were measured by reverse-transcription PCR and ELISA. The results demonstrated that PEG-PE-cationic-liposome-conjugated adenovirus could prolong the expression of the therapeutic gene in vivo and may enhance the antitumour efficacy.

High CC chemokine receptor 7 expression improves postoperative prognosis of lung adenocarcinoma patients

“…Many reports have revealed that the expression of the chemokine receptor CCR7 on cancer cells induces metastasis to regional lymph nodes (Müller et al , 2001; Andre et al , 2006; Cabioglu et al , 2007; Koizumi et al , 2007). On the other hand, Cao et al (2007) reported an antitumour effect of CCL19. Therefore, we became interested in the function of the CCR7–ligands axis, which appears to be associated with both good and bad outcomes in cancer prognosis.…”

Proteomic Biomarkers of Non-Small Cell Lung Cancer Patients

“…The proteomic study by Yang et al [22] identified three serum candidate protein biomarkers for NSCLC: apolipoprotein C-I (ApoC-I), haptoglobin alpha-1 chain, and www.journals.viamedica.pl S100A4, which can diagnose NSCLC in patients with a sensitivity and specificity of 96.56% and 94.79%, respectively. ApoC-I is a lipid carrier protein and, although previous studies mainly focused on lipoprotein metabolism, it has been reported that the ApoC-I also regulates many cellular functions such as the promotion of growth factor-mediated cell survival and apoptosis [23]. It has been demonstrated that ApoC-I has a certain anticancer effect on tumor cells, as well as the ability to decrease the expression of PCNA, Ki-67 and Bcl-2 proteins, enhance Bax protein expression, and inhibit cell proliferation [24].…”

Adenoviral Vector Immunity: Its Implications and Circumvention Strategies

“…Liposomes, both cationic and anionic, have also been applied for encapsulation of Ad [146–148]. Recently, Ad encapsulated in anionic liposomes demonstrated high transduction efficiency in a CAR-deficient cell line, evaded vector-specific NAbs and elicited lesser cytotoxicity as compared to Ad complexed with cationic liposomes [149].…”