Roth Research Laboratory

A new approach to treating metastatic non-small cell lung cancer (NSCLC) published open access: TUSC2 immunogene enhances efficacy of chemo­immuno combination on KRAS/LKB1 mutant NSCLC in humanized mouse model

https://www.nature.com/articles/s42003-022-03103-7.epdf?sharing_token=AI2c7KoJwZnD6sWpPj-0q9RgN0jAjWel9jnR3ZoTv0NYWfy6ADTiQNZDlzSIUzkMa6GgFDoY8J1a47spSvBV-_g4gg09bR-ZXyVl0mJue7p-XIHwOdcTUlwjgX4Y6RM2mY5I421-zDG8qpD7VIUk_CkN_pUz-obaGGsKhRD9Als%3D

Although the addition of checkpoint blockade to chemotherapy as first-line treatment has improved survival in stage 4 NSCLC, the majority of patients recur after 30 months. The TUSC2 gene encapsulated in nanovesicles and injected intravenously selectively kills cancer cells and augments the anti-tumor immune response. This preclinical study showed that the addition of immunogene therapy improves the efficacy of checkpoint blockade + chemotherapy. Complete responses were observed in humanized mice with metastatic human KRAS/LKB1 mutant NSCLC.

Immunoprofiling of the tumor microenvironment showed the addition of TUSC2 mediates: (a) infiltration of cytotoxic T cells, natural killer cells, and dendritic cells; (b) induction of antigen-specific T cell responses; (c) enrichment of central and memory effector T cells and (d) decreased levels of PD-1+ T cells, myeloid-derived sup­pressor cells, Tregs, and M2 tumor associated macrophages. Depletion studies showed the presence of functional central and memory effector T cells are required for efficacy.