# Induction of Immunological Antitumor Effects by the Combination of Adenovirus-Mediated Gene Transfer of B7-1 and Anti-Programmed Cell Death-1 Antibody in a Murine Squamous Cell Carcinoma Model

**Authors:** Makiko Hara, Sumiyo Saburi, Natsumi Uehara, Takahiro Tsujikawa, Mie Kubo, Tatsuya Furukawa, Masanori Teshima, Hirotaka Shinomiya, Shigeru Hirano, Ken-ichi Nibu

PMC · DOI: 10.3390/cancers16071359 · 2024-03-30

## TL;DR

This study shows that combining a gene therapy with an immune checkpoint inhibitor can boost the immune system's attack on a type of mouse head and neck cancer.

## Contribution

The study demonstrates a novel combination of B7-1 gene transfer and anti-PD-1 antibody to enhance antitumor immunity in squamous cell carcinoma.

## Key findings

- Combined AdB7 and anti-PD1 treatment significantly reduced tumor size in mice.
- Treatment increased immune cell density and Ki-67+ CD8+ T cells while decreasing regulatory T cells.
- AdB7-infected tumors overexpressed CD80 and showed increased IFN-gamma in T cells.

## Abstract

Head and neck cancer is the seventh most common cancer and most cases of head and neck cancer are squamous cell carcinoma (SCC). Recently, immune checkpoint inhibitors (ICPIs) such as anti-programmed cell death-1 (PD-1) have been developed. The aim of our study was to evaluate the antitumor effect of adenoviral vector carrying B7-1 (AdB7) in a murine SCC model in order to further explore the potential of the B7-1 gene in immunotherapy for head and neck cancers. Results indicated that tumor size was significantly reduced in the mice treated with both AdB7 and anti-mouse PD-1 antibody. Additionally, treatment resulted in significantly increased cell densities of total immune cells and Ki-67+ CD8+ T cells and decreased the number of regulatory T cells. Our findings indicate that adenovirus-mediated B7-1 gene expression may enhance the antitumor effect of antiPD1 against SCC.

Background: The goal of this study was to evaluate the antitumor immune effects of B7-1 gene expression in addition to immune checkpoint inhibitor against squamous cell carcinoma. Methods: A murine SCC cell line, KLN205, was infected with adenoviral vector carrying B7-1 (AdB7). Infected cells were injected subcutaneously in the flanks of DBA/2 mice. Three weeks after implantation, anti-mouse PD-1 antibody (antiPD1) was intraperitonially administrated twice a week for a total of six times. Results: CD80 was significantly overexpressed in the AdB7-infected tumors. IFN-gamma in the T cells in the spleen was significantly increased and tumor size was significantly reduced in the mice treated with both AdB7 and antiPD1. Targeted tumors treated with both AdB7 and antiPD1 exhibited significantly increased cell densities of total immune cells as well as Ki-67+ CD8+ T cells and decreased regulatory T cells. Conclusions: These results suggest that the B7-1 gene transfer may enhance the antitumor effect of anti-PD1 antibody against SCC.

## Linked entities

- **Genes:** CD80 (CD80 molecule) [NCBI Gene 941], CD80 (CD80 molecule) [NCBI Gene 941], PDCD1 (programmed cell death 1) [NCBI Gene 5133]
- **Proteins:** IFNA3 (interferon), Mki67 (antigen identified by monoclonal antibody Ki 67), CD8A (CD8 subunit alpha)
- **Diseases:** head and neck cancer (MONDO:0005627), squamous cell carcinoma (MONDO:0005096)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Cd80 (CD80 antigen) [NCBI Gene 12519] {aka B71, Cd28l, Ly-53, Ly53, MIC17, TSA1}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345] {aka D630048A14Rik, Ki-67, Ki67}, Pdcd1 (programmed cell death 1) [NCBI Gene 18566] {aka Ly101, PD-1, Pdc1}
- **Diseases:** Squamous Cell Carcinoma (MESH:D002294), tumor (MESH:D009369)
- **Species:** Adenoviridae (family) [taxon 10508], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** /2 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_A628), AdB7 — Phodopus sungorus (Striped hairy-footed hamster), Transformed cell line (CVCL_4V33), KLN205 — Mus musculus (Mouse), Squamous cell carcinoma of the mouse pulmonary system, Cancer cell line (CVCL_3533)

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11010972/full.md

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Source: https://tomesphere.com/paper/PMC11010972