Next-generation Tumor-homing Induced Neural Stem Cells as an Adjuvant to Radiation for the Treatment of Metastatic Lung Cancer.

Journal Article (Journal Article)

The spread of non-small cell lung cancer (NSCLC) to the leptomeninges is devastating with a median survival of only a few months. Radiation offers symptomatic relief, but new adjuvant therapies are desperately needed. Spheroidal, human induced neural stem cells (hiNeuroS) secreting the cytotoxic protein, TRAIL, have innate tumoritropic properties. Herein, we provide evidence that hiNeuroS-TRAIL cells can migrate to and suppress growth of NSCLC metastases in combination with radiation. In vitro cell tracking and post-mortem tissue analysis showed that hiNeuroS-TRAIL cells migrate to NSCLC tumors. Importantly, isobolographic analysis suggests that TRAIL with radiation has a synergistic cytotoxic effect on NSCLC tumors. In vivo, mice treated with radiation and hiNeuroS-TRAIL showed significant (36.6%) improvements in median survival compared to controls. Finally, bulk mRNA sequencing analysis showed both NSCLC and hiNeuroS-TRAIL cells showed changes in genes involved in migration following radiation. Overall, hiNeuroS-TRAIL cells +/- radiation have the capacity to treat NSCLC metastases.

Full Text

Duke Authors

Cited Authors

  • Mercer-Smith, AR; Buckley, A; Valdivia, A; Jiang, W; Thang, M; Bell, N; Kumar, RJ; Bomba, HN; Woodell, AS; Luo, J; Floyd, SR; Hingtgen, SD

Published Date

  • April 19, 2022

Published In

PubMed ID

  • 35441348

Electronic International Standard Serial Number (EISSN)

  • 2629-3277

Digital Object Identifier (DOI)

  • 10.1007/s12015-022-10375-3

Language

  • eng

Conference Location

  • United States