Zhang Yanna, Li Qian, Liu Nanxi, Hu Jianchuan, Lin Xiaojuan, Huang Meijuan, Wei Yuquan, Qi Xiaorong, Chen Xiancheng
Department of Blood Transfusion, Sichuan Provincial People's Hospital University of Electronic Science and Technology of China Chengdu Sichuan China.
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy West China Hospital, Sichuan University Chengdu China.
Bioeng Transl Med. 2023 Jun 24;8(5):e10554. doi: 10.1002/btm2.10554. eCollection 2023 Sep.
There 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 ( < 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/JCHAINNKT 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.
必须做出选择，制定一种安全可行的策略来应对难治性肿瘤和新冠病毒变体的逃逸动态，而基于干细胞的方案可能更可靠，因为它具有重置多功能免疫以应对进行性肿瘤和不断演变的病毒的独特能力。在本研究中，将来自成熟体细胞的球体 - 类胚体干细胞工程化为多功能生物制剂（3D - E/BSC），并接种到老年恒河猴体内，以确定针对病毒变体免疫逃逸的安全潜力。与此同时，一组符合条件的IV期非小细胞肺癌患者被批准进行I期临床试验。随后，通过灵长类动物试验和临床试验验证了其长期安全性和有效性（<0.01），即它不仅可以刺激血清学免疫，还能在3D - E/BSC撤离后重置宿主的核心免疫以应对变体逃逸。特别地，通过单细胞进化轨迹表明，3D - E/BSC已安全地重置了衰老宿主的老年胸腺，通过重新排列幼稚节律来重塑核心免疫，以进化TRGC2/JCHAIN NKT簇，同时激活NSCLC和COVID - 19的路径反馈，消除肿瘤和病毒逃逸动态，从而持续阻断病毒突变体的突破性感染，并使三分之一的晚期患者无需辅助治疗即可长期存活。我们的研究可能开创一种实用的多功能策略，以消除新冠病毒变体和难治性非小细胞肺癌的逃逸，从而使患者重新开始新的生命等式。
