Development of virus-like particles (VLPs) expressing human epidermal growth factor receptor-2 (HER2) for targeted cancer immunotherapy
Presenter(s)
Emma Creen and Sarah Maggiore
Abstract
Breast cancer is the most common type of cancer diagnosed in women in the United States. In patients with breast cancer, upregulated expression of the human epidermal growth factor receptor 2 (HER2) protein occurs in approximately 30% of breast cancer tissues. HER2 is a transmembrane glycoprotein receptor of the epidermal growth factor receptor (EGFR) family. EGFRs regulate cell proliferation, survival, and differentiation. HER2 overexpression is associated with increased signaling and correlates with poor prognosis. Expression of Ebola virus VP40 and glycoprotein (GP) in 293T cells will produce virus-like particles (VLPs) coated with GP. The Ebola virus GP functions as the viral attachment protein and mediates entry into antigen-presenting cells (APCs). Ebola VLPs expressing GP activate treated APCs inducing antigen-specific immune responses. Adjuvants have been used to improve a VLPs ability to activate an immune response. Retinoic acid inducible gene I (RIG I) functions as a cytoplasmic pattern recognition receptor that recognizes viral infection and induces the production of interferon. Interferon enhances antigen presentation and immune responses. We therefore hypothesize that VLPs expressing HER2, GP, and caRIG I (a constitutively active form of RIG I), induce a stronger anti-HER2 immune response from treated APCs than VLPs containing a mutant inactive form of RIG I (muRIG I). The goal of our present study is to generate HER2 containing VLPs and test whether they can target and activate APCs. VLPs were produced by co-transfecting 293T cells with vectors expressing chimeric caRIG I-VP40 or muRIG I-VP40, HER2, and GP genes. HER2 was shown to be expressed in HER2-expression-plasmid-transfected 293T cells and VLPs produced via expression of caRIG I VP40 or muRIG I, HER2, beta-lactamase and GP or GPF88A, an entry mutant of GP. However, VLP incorporated HER2 had a molecular weight of approximately 110 kDa compared to 160 kDa expressed from 293T cells. In future experiments we will test whether HER2 was cleaved post-transfection. Furthermore, we will test whether HER2 containing VLPs can stimulate APCs.
College
College of Science & Engineering
Department
Biology
Campus
Winona
First Advisor/Mentor
Osvaldo Martinez
Location
Kryzsko Great River Ballroom, Winona, Minnesota; United States
Start Date
4-23-2026 1:00 PM
End Date
4-23-2026 2:00 PM
Presentation Type
Poster Session
Format of Presentation or Performance
In-Person
Session
2a=1pm-2pm
Poster Number
35
Development of virus-like particles (VLPs) expressing human epidermal growth factor receptor-2 (HER2) for targeted cancer immunotherapy
Kryzsko Great River Ballroom, Winona, Minnesota; United States
Breast cancer is the most common type of cancer diagnosed in women in the United States. In patients with breast cancer, upregulated expression of the human epidermal growth factor receptor 2 (HER2) protein occurs in approximately 30% of breast cancer tissues. HER2 is a transmembrane glycoprotein receptor of the epidermal growth factor receptor (EGFR) family. EGFRs regulate cell proliferation, survival, and differentiation. HER2 overexpression is associated with increased signaling and correlates with poor prognosis. Expression of Ebola virus VP40 and glycoprotein (GP) in 293T cells will produce virus-like particles (VLPs) coated with GP. The Ebola virus GP functions as the viral attachment protein and mediates entry into antigen-presenting cells (APCs). Ebola VLPs expressing GP activate treated APCs inducing antigen-specific immune responses. Adjuvants have been used to improve a VLPs ability to activate an immune response. Retinoic acid inducible gene I (RIG I) functions as a cytoplasmic pattern recognition receptor that recognizes viral infection and induces the production of interferon. Interferon enhances antigen presentation and immune responses. We therefore hypothesize that VLPs expressing HER2, GP, and caRIG I (a constitutively active form of RIG I), induce a stronger anti-HER2 immune response from treated APCs than VLPs containing a mutant inactive form of RIG I (muRIG I). The goal of our present study is to generate HER2 containing VLPs and test whether they can target and activate APCs. VLPs were produced by co-transfecting 293T cells with vectors expressing chimeric caRIG I-VP40 or muRIG I-VP40, HER2, and GP genes. HER2 was shown to be expressed in HER2-expression-plasmid-transfected 293T cells and VLPs produced via expression of caRIG I VP40 or muRIG I, HER2, beta-lactamase and GP or GPF88A, an entry mutant of GP. However, VLP incorporated HER2 had a molecular weight of approximately 110 kDa compared to 160 kDa expressed from 293T cells. In future experiments we will test whether HER2 was cleaved post-transfection. Furthermore, we will test whether HER2 containing VLPs can stimulate APCs.
Comments
Creen, Emma E; Maggiore, Sarah R