Enhanced tumor immunogenicity through coupling cytokine expression with antigen presentation

Abstract

The density of tumor antigen in conjunction with major histocompatibility complex (MHC) class I molecules on the cell surface affects cytotoxic T cell (CTL) function in an active antitumor immune response. Thus, methods to enhance antigen expression/ presentation could augment the effect of cancer immune therapy. In the present study, we investigated the feasibility of modifying a cytokine signal peptide with a tumor antigenic epitope. We inserted the genes encoding the MHC class I-restricted antigenic epitope of chicken ovalbumin and tyrosinase-related protein 2 into the signal sequence of the interleukin-2 gene, replacing part of the signal sequence at different positions. Our results showed that these modified signal peptides still functioned, as indicated by cytokine secretion. The antigenic epitope within the modified signal peptide could be processed properly and presented on tumor cell surface. Tumor cells demonstrated enhanced immunogenicity as indicated by increased susceptibility to CTL lysis in vitro and decreased tumor grow in vivo after gene modification. These data provide potential perspectives in designing therapeutic or vaccine strategies in immuno-gene therapy of cancer.

Dairy-Derived and Egg White Proteins in Enhancing Immune System Against COVID-19

“…Heat-denatured ovalbumin also modulates interleukins' (IL) production by downregulating IL-4 and upregulating IL-10, 12, and 17. Ovalbumin-derived peptides corresponding to amino acids in position 77–84 and 126–134 also enhances the phagocytic activity of macrophages ( 57 ) and are reported to enhance immunotherapy ( 50 , 53 , 58 ). Ovotransferrin, another egg white protein, has been shown to stimulate the production of IL-6 and metalloproteinase (MMP) in HD 11 chicken macrophages ( 59 ).…”

Advances in the Value of Eggs and Egg Components for Human Health

“…Several egg white proteins and peptides have demonstrated immunomodulating activity. Ovalbumin has been found to induce the release of tumor necrosis factor (TNF) α in a dose-dependent manner in vitro, when modified with dicarbonyl methylglyoxyl (), and immunogenic ovalbumin peptides have been used to enhance immune responses for cancer immunotherapy ( − ). Tezuka and Yoshikawa () found that the phagocytic activity of macrophages was increased by the addition of ovalbumin peptides, OA 77−84 and OA 126−134, derived from peptic and chymotryptic digestions, respectively.…”

Antitumor effect and underlying mechanism of RGD-modified adenovirus mediated IL-24 expression on myeloid leukemia cells

“…Cytokine-based tumor immuno-gene therapy has been intensively investigated in order to develop effective cancer therapy methods [18]. A requisite component for improving gene-based therapies includes tumor suppressor genes that exhibit cancer constrained inhibitory activity.…”

“…In brief, the K562, THP-1, and MEG-01 cells were infected with recombinant adenoviruses for 48 h and then collected to extract the total RNA with Trizol Reagent (Invitrogen, Carlsbad, CA, USA). The first cDNA strand was synthesized using Oligo d(T) 18 . The PCR primers specific for IL-24 were described above.…”