Delivery of human NKG2D-IL-15 fusion gene by chitosan nanoparticles to enhance antitumor immunity

Wang

J Biomedical Materials Res

et al. 2016

Hepatocellular carcinoma (HCC) is the fifth most prevalent malignancy and the third leading cause of cancer-related deaths worldwide. More effective cures for HCC patients are urgently needed, of which gene therapy is among those with the most potential. We previously developed a novel gene carrier by conjugating low molecular weight chitosan with TAT (transactivator of transcription) peptide and LHRH (luteinizing hormone-releasing hormone) analog, with the resultant TAT-LHRH-chitosan conjugate (TLC) demonstrating high selectivity for hepatoma cells in vitro. However, it remains unclear whether TLC can deliver the genes to the target organs and tissues in vivo, which is one of the critical features determining their medical application potential. The current study further investigated the in vivo distribution of TLC/DNA nanoparticles (TLCDNPs) in the nude mice with subcutaneous hepatoma xenografts. It was found that TLCDNPs delayed the renal clearance of DNA and prolonged its circulation time as compared with CS/DNA complexes (CDNPs) and naked DNA, but failed to demonstrate enhanced accumulation of DNA in the hepatoma xenografts. The mechanisms regarding the failure of TLCDNPs' tumor targeting in the mice bearing subcutaneous hepatoma xenografts remain unclear and need to be further addressed. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2394-2400, 2016.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Biodistribution of TAT‐LHRH conjugated chitosan/DNA nanoparticles in the mice bearing hepatoma xenografts

Wang

J Biomedical Materials Res

et al. 2016

Immune Response Activation and Immunomodulation

“…Due to the self-regulation nature of polycations and polyanions, it leads to the formation of linking complexes between TPP groups and chitosan amino groups. In the process of the protonation of the chitosan at physiological pH, TPP is covalently bound to chitosan amino groups providing structural change and better provocation [23,50,61,67,68].…”

Section: Chitosanmentioning

confidence: 99%

Current State of the Art in DNA Vaccine Delivery and Molecular Adjuvants: Bcl-xL Anti-Apoptotic Protein as a Molecular Adjuvant

Gülce-İz¹,

Sağlam-Metiner²

2019

DNA vaccines (nucleic acid vaccines) have been gaining importance as promising therapeutics against infectious diseases, cancer, autoimmune disorders and allergy for the past two decades. However, the immune responses elicited by the DNA vaccines are not at the desired level to stimulate a protective immune response. Thus, studies are focused on the enhancement of DNA vaccine-induced immune response by different approaches. The most common approach is to use biomaterial-based adjuvants for enhanced antigen delivery and uptake by antigenpresenting cells. Some of these adjuvants are alum, saponins, microspheres, nanoparticles, liposomes, polymers, etc. used in vaccine formulations. In addition, molecular adjuvants like cytokines, chemokines and heat shock proteins have been shown to be promising in designing DNA vaccines. In this chapter, molecular adjuvants to improve DNA vaccination-induced immune responses will be summarized with a special focus on Bcl-xL anti-apoptotic protein.

“…Its efficiency in suppressing cancer growth was better than IL-15 cytokine therapy alone. They also delivered their fusion gene into tumor cells by loading the DNA with chitosan nanoparticles [ 77 ]. Tumor cells uptaking the nanoparticles with the fusion gene stimulated NK cells and CD8+ T cells in vitro.…”

Section: Strategies Of Fusion Proteinsmentioning

confidence: 99%

Fusion Proteins of NKG2D/NKG2DL in Cancer Immunotherapy

Ding

Yang

Wei

2018

IJMS

NKG2D (natural killer group 2, member D) is an important activating receptor in natural killer (NK) cells and some T cells. NKG2D ligands (NKG2DLs) are specifically expressed on most tumor cells. The engagement of these ligands on tumor cells to NKG2D on NK cells will induce cell-mediated cytotoxicity and have target cells destroyed. This gives NKG2D/NKG2DLs great potential in cancer therapeutic application. The creation of NKG2D/NKG2DL-based multi-functional fusion proteins is becoming one of the most promising strategies in immunotherapy for cancer. Antibodies, cytokines, and death receptors have been fused with NKG2D or its ligands to produce many powerful fusion proteins, including NKG2D-based chimeric antigen receptors (CARs). In this article, we review the recent developments of the fusion proteins with NKG2D/NKG2DL ligands in cancer immunotherapy.