Characteristics of a CCL21-gene modified dendritic cell vaccine utilized for a clinical trial in non-small cell lung cancer.

The treatment of non-small cell lung cancer has made major strides with the use of immune checkpoint inhibitors, but there remains a significant need for therapies that can overcome immunotherapy resistance. Dendritic cell (DC) vaccines have been proposed as a therapy that can potentially enhance the antitumor immune response. We have embarked on a phase I clinical trial of a vaccine consisting of monocyte-derived DCs (moDCs) modified to express the chemokine CCL21 (CCL21-DC) given in combination with pembrolizumab.

Noninvasive Lung Cancer Subtype Classification Using Tumor-Derived Signatures and cfDNA Methylome.

Unlabelled: Accurate diagnosis of lung cancer is important for treatment decision-making. Tumor biopsy and histologic examination are the standard for determining histologic lung cancer subtypes. Liquid biopsy, particularly cell-free DNA (cfDNA), has recently shown promising results in cancer detection and classification.

Single-stranded pre-methylated 5mC adapters uncover the methylation profile of plasma ultrashort Single-stranded cell-free DNA.

Whole-genome bisulfite sequencing (BS-Seq) measures cytosine methylation changes at single-base resolution and can be used to profile cell-free DNA (cfDNA). In plasma, ultrashort single-stranded cfDNA (uscfDNA, ∼50 nt) has been identified together with 167 bp double-stranded mononucleosomal cell-free DNA (mncfDNA). However, the methylation profile of uscfDNA has not been described.

CXCL9/10-engineered dendritic cells promote T cell activation and enhance immune checkpoint blockade for lung cancer.

Immune checkpoint blockade (ICB) with PD-1/PD-L1 inhibition has revolutionized the treatment of non-small cell lung cancer (NSCLC). Durable responses, however, are observed only in a subpopulation of patients. Defective antigen presentation and an immunosuppressive tumor microenvironment (TME) can lead to deficient T cell recruitment and ICB resistance.

CCL21-DC in situ vaccination in murine NSCLC overcomes resistance to immunotherapy and generates systemic tumor-specific immunity.

Background: Despite recent advances in immunotherapy, many patients with non-small cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICI). Resistance to ICI may be driven by suboptimal priming of antitumor T lymphocytes due to poor antigen presentation as well as their exclusion and impairment by the immunosuppressive tumor microenvironment (TME). In a recent phase I trial in patients with NSCLC, in situ vaccination (ISV) with dendritic cells engineered to secrete CCL21 (CCL21-DC), a chemokine that facilitates the recruitment of T cells and DC, promoted T lymphocyte tumor infiltration and PD-L1 upregulation.