UCLA researchers from the Department of Medicine, Pathology, & Laboratory Medicine and Molecular & Medical Pharmacology have identified a novel cell-based therapy that leads to enhanced immunotherapy efficacy and overcomes treatment resistance to immune checkpoint blockade in non-small cell lung cancer.
BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, making up approximately 85% of all lung cancers. Standard treatment for NSCLC is immune checkpoint blockade (ICB) with Programed Death-1/Programmed Death-Ligand 1 (PD-1/PD-L1) inhibition. PD-L1 is a protein on cancer cells that can bind to PD-1 on T cells and inhibit anti-tumor immunity. Thus, ICB aims to enhance immune recognition and destruction of cancer cells. However, only a subpopulation of patients exhibits durable responses due to defective antigen presentation and an immunosuppressive tumor microenvironment. Therefore, it is critical to supplement current frontline immunotherapies with novel methods that can increase efficiency of ICB and overcome treatment resistance by fully engaging endogenous immunity of the patient.
INNOVATION: UCLA researchers have developed a cell-based intratumoral therapy that can overcome resistance to ICB. This therapy consists of engineered immune cells that are administered via in situ vaccination. They found that administering this therapy led to enhanced T cell infiltration and activation in the tumor microenvironment, resulting in effective tumor inhibition in multiple syngeneic mouse models of NSCLC. The developed therapy established a system for tumor-specific immunity. Thus, supplementing ICB immunotherapy for NSCLC with this novel intratumoral therapy may significantly boost patient response rates and minimize treatment resistance.
POTENTIAL APPLICATIONS:
- Supplementing ICB in the treatment of NSCLC to improve efficacy
- Treatment of ICB-resistant tumors
- Provides a mechanistic understanding of host immune activation via the specific cell types in this therapy
ADVANTAGES:
- Works synergistically with the current frontline treatment for NSCLC
- Harnesses the patient’s endogenous immune system against the tumor
- Diminishes immunosuppressive conditions leading to ICB therapy resistance
DEVELOPMENT-TO-DATE: UCLA researchers have developed an intratumoral cell-based therapy that in combination with immune checkpoint blockade, can overcome treatment resistance and enhance anti-tumor immunity in non-small cell lung cancer mouse models.
Related Papers (from the inventors only):
Lim, R. J. et al. CXCL9/10-engineered dendritic cells promote T cell activation and enhance immune checkpoint blockade for lung cancer. Cell Reports Medicine 5, 101479 (2024).
Keywords: Non-small cell lung cancer, treatment resistance, immune checkpoint blockade, immunotherapy, cell-based therapy, anti-tumor immunity, tumor microenvironment, vaccination