Author of

• 25919

  +

  MA27 - Novel Drugs and PDX Models (ID 931)

  • Event: WCLC 2018
  • Type: Mini Oral Abstract Session
  • Track: Targeted Therapy
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/26/2018, 13:30 - 15:00, Room 206 BD

  • 26215

    +

    MA27.05 - Drug Loaded Mesenchymal Stem Cells for Targeted Lung Cancer Treatment in Mice (ID 11827)

    14:00 - 14:05  |  Author(s): Xusheng Wang
    • Abstract

    Background
    

    Mesenchymal stem cells (MSCs) are cells residing in many tissues of our body. Due to their low immunogenicity, allogeneic MSCs have been used extensively for immune regulation and many other conditions. Over 90% of culture expanded MSCs are entrapped in the lungs after intravenous infusion. Taking this advantage, in this study, we utilized MSCs as a vehicle for targeted delivery of drugs to the lungs to treat lung cancer.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    For enhanced cellular uptake, docetaxel (DTX) was loaded in PLGA-PEG nanoparticles (NPs). Lung cancer was induced in Kras^G12D mice, who expressed a form of constitutively activated Kras protein in lung cells upon local administration of cre-advenovirus (AdCre) solution. The size of lung cancer was assessed by PET-CT and tissue analysis.

    4c3880bb027f159e801041b1021e88e8 Result
    

    The amount of DTX uptake by MSCs at 1, 3, 7, 12, and 24 hours was measured by LC-MS, and the result showed that DTX intake reached peak at 12 hours with ~36 μg in 10⁶ MSCs, compared to 15 μg DTX in equal number of fibroblasts, indicating that MSCs had higher NPs-DTX uptake capacity than fibroblasts. To visualize MSCs in vivo, MSCs were labeled with luciferase (Luci). 10⁶ MSCs-Luci loaded with NPs-DTX were injected intravenously in mice. In vivo imaging system (IVIS) analysis showed a predominant accumulation of the cells (drug) in the lungs at 24 hours after injection. The effect of MSCs/NPs/DTX in inhibiting lung cancer development was evaluated in Kras^G12D mice. Five days after lung cancer induction, the mice received an intravenous injection of 10⁶ MSCs loaded with NPs-DTX (~25 μg), NPs-DTX (~200 μg) alone, or PBS every 5 days. 30 days after tumor induction, PET-CT analysis detected large masses in the lungs in PBS treated mice, compared to much smaller masses in MSCs/NPs/DTX-treated or NPs-DTX-treated mice. In consistence, the tumor weight was significantly lower in MSCs/NPs/DTX-treated or NPs-DTX-treated animals than PBS-treated mice, and similar reductions in tumor weight were found in MSCs/NPs/DTX-treated or NPs-DTX-treated mice.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Thus our data indicate that MSC loaded with DTX can provide targeted therapy for lung cancer to achieve equal cancer inhibition with much lower doses of DTX thus reducing side effects of the drug. As allogeneic MSCs do not cause obvious immune rejection, our study suggests a novel approach for targeted lung cancer therapy.

    6f8b794f3246b0c1e1780bb4d4d5dc53