For a study, researchers sought to research the progression and metastasis of lung cancer; they used in-vitro cell models. These models—which are often 2D cell cultures—are not accurate representations of the intricacy of cancer and the interactions between cells in reality. An appealing alternative to chemotherapy or radiation therapy for the management of lung cancer is immune therapy. They created a 3D model of lung cancer using layers of immunological, bronchial epithelial, fibroblastic, epithelial, and lung adenocarcinoma cells cultured in matrigel.

Evaluation of the genes increased in the 3D culture led to the production of an antibody against a particular overexpressed protein. It assessed how well the generated antibody affected gene expression and cell indicators. The use of flow cytometry was used to analyze the expression of cell markers. Immune cells that had been stimulated and grown ex vivo against an immunogenic epitope of the protein-target were used to make the antibody. Utilizing gene and flow cytometry analyses, antibody efficiency was estimated.

Genetic investigation revealed several overexpressed genes; BMPR2 was one of them, and it was chosen as the antibody target. Epcam, an overexpressed marker in lung cancer, and Notch were shown to be expressed more often in lung cancer models (promotes tumor initiation). Analysis of the immune cell population alone revealed higher expression of CD25 (activated T and B cells), CD80/86 (APC), CD206 (macrophages), and CTLA4 (down-regulation of the immune system). Anti-BMPR2 antibody incubation of the lung model resulted in reduced cell growth, enhanced immunological marker expression (CD206), and decreased expression of cancer-progression-related genes (CD44, FOS, NRAS, ARAF).

A 3D cell culture model for lung cancer had been created by investigators. They have discovered a possible immunotherapy target and created an antibody against the particular target. It was discovered that the addition of an anti-BMPR2 antibody raised the expression of genes involved in immune activation and lowered the expression of genes involved in tumor growth in our lung cancer model. The antibody had the potential to be a cutting-edge therapeutic antibody for the treatment of lung cancer.

Reference: annalsofoncology.org/article/S0923-7534(22)01895-6/fulltext