Combination Cancer Immunotherapy with Dendritic Cell Vaccine and Nanoparticles Loaded with Interleukin-15 and Anti-beta-catenin siRNA Significantly Inhibits Cancer Growth and Induces Anti-Tumor Immune Response.

Abstract

PURPOSE:

The invention and application of new immunotherapeutic methods can compensate for the inefficiency of conventional cancer treatment approaches, partly due to the inhibitory microenvironment of the tumor. In this study, we tried to inhibit the growth of cancer cells and induce anti-tumor immune responses by silencing the expression of the β-catenin in the tumor microenvironment and transmitting interleukin (IL)-15 cytokine to provide optimal conditions for the dendritic cell (DC) vaccine.

METHODS:

For this purpose, we used folic acid (FA)-conjugated SPION-carboxymethyl dextran (CMD) chitosan (C) nanoparticles (NPs) to deliver anti-β-catenin siRNA and IL-15 to cancer cells.

RESULTS:

The results showed that the codelivery of β-catenin siRNA and IL-15 significantly reduced the growth of cancer cells and increased the immune response. The treatment also considerably stimulated the performance of the DC vaccine in triggering anti-tumor immunity, which inhibited tumor development and increased survival in mice in two different cancer models.

CONCLUSIONS:

These findings suggest that the use of new nanocarriers such as SPION-C-CMD-FA could be an effective way to use as a novel combination therapy consisting of β-catenin siRNA, IL-15, and DC vaccine to treat cancer.

• Authors: Armin Mahmoud Salehi Kheshti, Farnaz Hajizadeh, Asal Barshidi, Bentolhoda Rashidi, Farbod Ebrahimi, Simin Bahmanpour, Vahid Karpisheh, Fatemeh Karimian Noukabadi, Fariba Karoon Kiani, Hadi Hassannia, Fatemeh Atyabi, Seyed Hossein Kiaie, Fatah Kashanchi, Jamshid Gholizadeh Navashenaq, Hamed Mohammadi, Rafieh Bagherifar, Reza Jafari, Naime Majidi Zolbanin, Farhad Jadidi-Niaragh
• Journal: Pharmaceutical research (Pharm Res) Vol. 39 Issue 2 Pg. 353-367 (Feb 2022) ISSN: 1573-904X [Electronic] United States
• PMID: 35166995 (Publication Type: Journal Article, Retracted Publication)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Antineoplastic Agents
• CTNNB1 protein, mouse
• Cancer Vaccines
• Drug Carriers
• Interleukin-15
• RNA, Small Interfering
• beta Catenin

Topics

• Animals
• Antineoplastic Agents (administration & dosage, chemistry)
• Cancer Vaccines (administration & dosage, immunology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Dendritic Cells (immunology, transplantation)
• Drug Carriers
• Drug Compounding
• Female
• Gene Expression Regulation, Neoplastic
• Interleukin-15 (administration & dosage, chemistry)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Magnetic Iron Oxide Nanoparticles
• Melanoma, Experimental (genetics, immunology, pathology, therapy)
• Mice, Inbred BALB C
• RNA, Small Interfering (administration & dosage, genetics)
• RNAi Therapeutics
• Skin Neoplasms (genetics, immunology, pathology, therapy)
• Tumor Burden (drug effects)
• Tumor Microenvironment
• beta Catenin (genetics)
• Mice