Related Experiment Video
Updated: Aug 22, 2025
Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
Published on: January 19, 2019
A Novel P53 Nanomedicine Reduces Immunosuppression and Augments Anti-PD-1 Therapy for Non-Small Cell Lung Cancer in
Sang-Soo Kim1,2, Joe B Harford2, Manish Moghe1
1Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
Abstract:
Lung cancer is among the most common and lethal cancers and warrants novel therapeutic approaches to improving patient outcomes. Although immune checkpoint inhibitors (ICIs) have demonstrated substantial clinical benefits, most patients remain unresponsive to currently approved ICIs or develop resistance after initial response. Many ongoing clinical studies are investigating combination therapies to address the limited efficacy of ICIs. Here, we have assessed whether p53 gene therapy via a tumor-targeting nanomedicine (termed SGT-53) can augment anti-programmed cell death-1 (PD-1) immunotherapy to expand its use in non-responding patients. Using syngeneic mouse models of lung cancers that are resistant to anti-PD-1, we demonstrate that restoration of normal p53 function potentiates anti-PD-1 to inhibit tumor growth and prolong survival of tumor-bearing animals. Our data indicate that SGT-53 can restore effective immune responses against lung cancer cells by reducing immuno-suppressive cells (M2 macrophages and regulatory T cells) and by downregulating immunosuppressive molecules (e.g., galectin-1, a negative regulator of T cell activation and survival) while increasing activity of cytotoxic T cells. These results suggest that combining SGT-53 with anti-PD-1 immunotherapy could increase the fraction of lung cancer patients that responds to anti-PD-1 therapy and support evaluation of this combination particularly in patients with ICI-resistant lung cancers.
Insights
p53 gene therapy with SGT-53 enhances anti-programmed cell death-1 (PD-1) immunotherapy in lung cancer. This combination overcomes resistance by restoring immune responses, improving tumor growth inhibition and survival in preclinical models.
Area of Science:
- Oncology
- Immunotherapy
- Gene Therapy
Background:
- Lung cancer remains a leading cause of cancer-related deaths, necessitating advanced therapeutic strategies.
- Immune checkpoint inhibitors (ICIs) show promise but have limited efficacy in many patients due to non-response or acquired resistance.
- Combination therapies are being explored to enhance ICI effectiveness.
Purpose of the Study:
- To investigate if p53 gene therapy using tumor-targeting nanomedicine (SGT-53) can enhance anti-programmed cell death-1 (PD-1) immunotherapy.
- To evaluate the efficacy of this combination in lung cancer models resistant to anti-PD-1 therapy.
Main Methods:
- Utilized syngeneic mouse models of anti-PD-1 resistant lung cancers.
- Administered SGT-53 (p53 gene therapy) in combination with anti-PD-1 immunotherapy.
- Assessed tumor growth, animal survival, and immune cell populations.
Main Results:
- Restoration of normal p53 function by SGT-53 potentiated anti-PD-1 therapy, inhibiting tumor growth and prolonging survival.
- The combination therapy reduced immunosuppressive M2 macrophages and regulatory T cells.
- It also downregulated immunosuppressive molecules like galectin-1 and increased cytotoxic T cell activity.
Conclusions:
- Combining SGT-53 with anti-PD-1 immunotherapy shows potential to overcome ICI resistance in lung cancer.
- This combination may expand the patient population benefiting from anti-PD-1 therapy, particularly those with resistant disease.
- Further evaluation in clinical settings is warranted.
Related Concept Videos
02:23Abnormal Proliferation
02:43Mouse Models of Cancer Study
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...