PD-1 cis-targeted IL-2v in combination with radiotherapy inhibits lung cancer growth and remodels the immune microenvironment.

Background: More efficient therapeutic options for non-small cell lung cancer (NSCLC) are needed as the survival at 5 years of metastatic disease is near zero. In this regard, we used a preclinical model of metastatic lung adenocarcinoma (SV2-OVA) to assess the safety and efficacy of novel radio-immunotherapy combining hypofractionated radiotherapy (HRT) with muPD1-IL2v immunocytokine and muFAP-CD40 bispecific antibody.

Methods: We evaluated the changes in the lung immune microenvironment at multiple timepoints following combination therapies and investigated their underlying antitumor mechanisms.

Cell Squeeze: driving more effective CD8 T-cell activation through cytosolic antigen delivery.

Cell Squeeze is a novel technology that relies on temporarily disrupting the cell membrane to deliver cargo directly into the cytosol. This approach is applicable to a broad range of cell types (peripheral blood mononuclear cells, red blood cells, hematopoietic stem cells, etc.) and cargos (peptides, proteins, small molecules, nucleic acids, and gene-editing complexes) while minimally disrupting normal cell function.

Combinations of Toll-like receptor 8 agonist TL8-506 activate human tumor-derived dendritic cells.

Background: Dendritic cells (DCs) are professional antigen presenting cells that initiate immune defense to pathogens and tumor cells. Human tumors contain only few DCs that mostly display a non-activated phenotype. Hence, activation of tumor-associated DCs may improve efficacy of cancer immunotherapies.

The tumor-targeted CD40 agonist CEA-CD40 promotes T cell priming via a dual mode of action by increasing antigen delivery to dendritic cells and enhancing their activation.

Tumor-targeted CD40 agonism represents an attractive strategy for cancer immunotherapy (CIT) as it promotes dendritic cell (DC) activation and concomitant tumor-specific T cell priming without causing systemic side effects. We developed the bispecific CD40 agonistic antibody CEA-CD40, which triggers CD40 stimulation exclusively in the presence of carcinoembryonic antigen (CEA), a glycoprotein specifically expressed on tumor cells. In this study, we demonstrate that CEA-CD40 can enable potent in vitro DC activation and consecutive T cell cross-priming in a CEA-specific manner.

Microfluidic Squeezing Enables MHC Class I Antigen Presentation by Diverse Immune Cells to Elicit CD8 T Cell Responses with Antitumor Activity.

CD8 T cell responses are the foundation of the recent clinical success of immunotherapy in oncologic indications. Although checkpoint inhibitors have enhanced the activity of existing CD8 T cell responses, therapeutic approaches to generate Ag-specific CD8 T cell responses have had limited success. Here, we demonstrate that cytosolic delivery of Ag through microfluidic squeezing enables MHC class I presentation to CD8 T cells by diverse cell types.