Cancer immunotherapy is one of the commonly used methods in the treatment of cancer. The aim of this approach is to strengthen or restore immune function for effective diagnosis of aberrant cells antigens. For this reason, cancer specific peptides or proteins are used as antigens to induce an immune response capable of removing cancer cells. Liposomal formulations are an important carrier system frequently used for delivery of antigen because the specific properties of this component such as lipid composition, charge, size, encapsulation of antigens, or adjuvants can be changed. Among different types of liposomal formulations, the use of cationic and pH-sensitive nanoliposomes has been markedly increased for liposome-based vaccines. In this review, we describe the properties of nanoliposomes as delivery systems for cancer immunotherapy.
Introduction: Inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) is an efficient strategy for lowering low-density lipoprotein cholesterol (LDL-C). There are, however, scant data on the efficacy and safety of PCSK9 inhibitors in non-cardiovascular diseases, particularly cancer. The present study aimed to evaluate the effect of PCSK9 inhibition using a nanoliposomal antiPCSK9 vaccine on cancer behavior and endpoints in mice bearing breast tumor. Material and methods: To induce antiPCSK9 antibody in vivo, a nanoliposomal antiPCSK9 vaccine absorbed on 0.4% alum adjuvant was used. To induce tumor, BALB/c mice were subcutaneously inoculated with 4T1 breast carcinoma cells. After the tumor mass was palpable (approximately 10 mm 3), the mice were randomly divided into four groups and subjected to different treatment protocols: (1) PBS (untreated control), (2) vaccine group, (3) combination of vaccine and Doxil, and (4) Doxil (positive control) group. Vaccine was subcutaneously administered to mice four times at 2-week intervals. Two weeks after the last administration, the vaccinated and non-vaccinated mice were subcutaneously inoculated with 4T1 breast carcinoma cells. To evaluate therapeutic efficacy, mouse body weight, tumor size, and survival were monitored every other day for 60 days. Results: The nanoliposomal antiPCSK9 vaccine was found to efficiently induce specific antibodies against PCSK9 in BALB/c mice, thereby decreasing plasma levels of PCSK9 and inhibiting its function. Tumor size analysis showed that time to reach endpoint (TTE) of the vaccine, combination, Doxil, and control groups was 47 ±10, 57 ±4, 60 ±4 and 39 ±9 days, respectively. Rate of tumor growth in vaccine, combination and Doxil groups was decreased by 21%, 48% and 53%, respectively, compared to the control group. Lifespan was increased by 4.2% in the vaccine group, compared with the Effects of immunization against PCSK9 in an experimental model of breast cancer Arch Med Sci 3, May / 2019 571 control group. Additionally, the survival in the combination and Doxil groups was significantly higher than the vaccine and control groups. Conclusions: Our results revealed that PCSK9 inhibition may moderately improve breast cancer outcomes while having no harmful effects in tumor-bearing mice.
Galbanic acid (Gba), a sesquiterpene coumarin , with strong antiangiogenic activity could serve as an excellent anti-cancer agent. However, Gba is a poor water-solube which hampered its clinical application. In this study, a pegylated liposomal Gba (PLGba) with HSPC/Cholesterol/mPEG 2000 -DSPE (56.2, 38.3, 5.3% molar ratio) was developed by the thin film hydration plus extrusion and calcium acetate gradient remote loading method, to address the issue of poor Gba solubility. Moreover, an integrin-targeting ligand (RGD peptide, cyclo[Arg-Gly-Asp-D-Tyr-Cys]) was post-inserted into liposomes in order to increase Gba cell delivery. Using fluorescently-labeled model liposomes, it was found that the targeting could improve the integrin-mediated cellular uptake of the liposomes in vitro in human umbilical vein endothelial cells (HUVECs), and in vivo as evidenced by chicken chorioallantoic membrane angiogenesis (CAM) model. It also could enrich the liposome accumulation in C26 tumor. Interestingly, co-treatment with PLGba and pegylated liposomal doxorubicin (PLD, also known as Doxil ® ) had a synergistic and antagonistic antiproliferative effect on the C26 tumor cell line and the normal HUVEC, respectively. In C26 tumor bearing BALB/c mice, the PLGba and PLD combinatorial therapy improved the antitumor efficacy of the treatment as compared to those of single agents. This results have clear implications for cancer therapy.
Introduction: Inhibition of proprotein convertase subtilisin/kexin 9 (PCSK9) is an effective therapeutic tool for lowering low-density lipoprotein cholesterol (LDL-C). There is no available evidence on the efficacy and safety of PCSK9 inhibitors in non-cardiovascular diseases, particularly cancer. The present study aimed to evaluate the effect of PCSK9 inhibition on cancer endpoints in mice bearing colon carcinoma, using a nanoliposomal antiPCSK9 vaccine. Material and methods: The prepared nanoliposomal antiPCSK9 vaccine was subcutaneously inoculated in BALB/c mice four times with a biweekly interval. Two weeks after the last booster, the vaccinated and unvaccinated mice were subcutaneously inoculated with CT26 colon cancer cells into the right flank. After the tumor mass became palpable, the mice were randomly divided into three groups: (1) PBS (untreated control), (2) vaccine group, and (3) pegylated liposomal doxorubicin (PLD; positive control) group. Body weight, tumor size and survival of mice were monitored for 50 days. Results: The nanoliposomal antiPCSK9 vaccine could efficiently provoke specific antibodies against PCSK9 in BALB/c mice and thereby reduced the plasma level and function of PCSK9. Tumor volume was 77% and 87.7% lower (p < 0.0001) in the vaccinated mice when compared with Doxil (liposomal doxorubicin) and control mice, respectively. Tumor size analysis showed that time to reach the endpoint of the vaccine group (47 ±11 days) was slightly but not significantly higher than PLD (46 ±2.6 days) and the control (43 ±12 days) groups. The tumor growth rates in the vaccine and PLD groups were reduced by 9.3% and 7.3, respectively, when compared with the control group. The vaccinated mice survived slightly but not significantly longer than PLD and the control mice. The median survival of the vaccine, PLD and control groups were 51, 45, and 41 days, respectively. The vaccinated mice's life was prolonged by 24.4% as compared with the control mice, while it was increased by 9.8% in the PLD group. Preparation of immunogenic peptide The Immunogenic Fused PCSK9-Tetanus (IFPT) peptide with a purity grade of > 95% was synthe-Conclusions: Our results revealed that PCSK9 inhibition not only exerted no harmful effects but also could moderately inhibit tumor growth, and improve lifespan and survival in mice bearing colon cancer.
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