Designing an engineered living material-based boosting ‘hub’ to maximize cytotoxicity of human immune cells against solid tumors

• Applicant: Archana Kaushik Yanamandra Guruvenkata
• Subject Area: Biomaterials ; Immunology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 520638706

Adoptive cell therapies (ACT) such as CAR-T or CAR-NK have emerged as the most effective form of immunotherapy where human cytotoxic immune cells (= killer cells) cells are isolated, expanded in vitro, genetically engineered by introducing chimeric antigen receptors (CAR), and infused back into the patients.Despite the great success in hematologic malignancies, the effectiveness of ACT in solid tumor is rather disappointing due to high costs involved, a lot of lethal side effects etc. The focus of most of the investigations using engineered immune cells in Engineered Living Materials (ELMs) was on addressing ways to enhance the proliferation of killer cells but the core issue of poor infiltration of killer cells into the tumor microenvironment and approaches to ameliorate this problem especially in solid tumors have not been addressed till now. This project aims to develop a Hyaluronic acid-based ELM encapsulated with engineered EGFR specific CAR-NK cells or MART-1 CTLs along with Polymer-Nanoparticles or poly lactic-co-glycolic acid (PLGA) microspheres with killer cell activating molecules (Yoda-1, IL-2, Nocodazole, Vinblastine) as the cargo. The activating molecules will enhance the infiltration and killing efficiency of human killer cells in melanoma (solid tumor) thus, the ELM acts as a "boosting center" for immune cells. Hence, the problems of high cell number, high costs involved, side effects such as cytokine storm associated with ACT can be circumvented by locally boosting the killing efficiency of engineered killer cells using ELMs.

• DFG Programme: Research Grants