Secure reversal of immune evasion from refractory NSCLC and highly contagious CoV‐2 mutants by using 3D‐engineered multifunctional biologics

AbstractThere is an imperative choice to develop a secure feasible strategy to address evasion dynamics of refractory tumors and SARS‐CoV‐2‐variants, while stem cell‐based protocol may be more reliable as its unique ability for resetting multifunctional immunity to address progressive tumor and the constantly‐evolving virus. In this study, spheroid‐embryonoid stem cells from mature somatic cells were engineered as multifunctional biologics (3D‐E/BSC) and inoculated in senile rhesus to identify secure potential against immune‐evasion from viral‐variants. Meanwhile, a cohort of eligible patients with stage IV NSCLC were approved for phase I clinical trials. Subsequently, long‐lasting security and efficacy were validated by primate and clinical trials (p < 0.01) in that it could not only stimulate serological immunity, but also reset core immunity for hosts to address variant evasion after 3D‐E/BSC withdrawal. Particularly, illustrated by single‐cell evolving trajectory, 3D‐E/BSC had securely reset senile thymus of aging hosts to remodel core immunity by rearranging naive rhythm to evolve TRGC2+/JCHAIN+NKT clusters to abolish tumoral and viral evasion dynamics with path‐feedbacks of NSCLC and COVID‐19 simultaneously activated, leading to continuous blockade of breakthrough infection of viral‐mutants and long‐term survival in one‐third of terminal patients without adjuvant required. Our study may pioneer a practical multifunctional strategy to eliminate evasion of SARS‐CoV‐2 variants and refractory NSCLC so as for victims to restart a new life‐equation.