Abstract Text: T-cell based therapy is well-known for hematological malignancies, while solid tumors still pose a challenge as they are localized, protected from circulating T-cells, and heterogeneous. Additionally, ex vivo genetic modification of large numbers of tumor-specific T-cells is elaborate, expensive and time consuming. We have developed a porous, biocompatible scaffold for immobilization of lentiviruses carrying tumor-specific antigen receptor genes. These scaffolds, when implanted subcutaneously in mice, show no systemic inflammation and facilitate preferential recruitment of T-cells. Engineered T-cells when co-cultured with tumor cells in vitro show tumor cell killing accompanied with increase in anti-tumor cytokines. These scaffolds, when implanted in tumor bearing mice, enable recruitment and transduction of host T-cells with tumor antigen specific receptors. Tumor-specific T-cells home towards tumor as well as secondary lymphoid organs, thereby, leading to significant reduction in tumor size and a systemic increase in anti-tumor cytokines. Here, a material-based engineering of T-cells to provide a localized approach for solid tumor T-cell based treatment is presented. This could be developed as an alternative to ex vivo genetic programming of T-cells.
