Therapeutic cell engineering with surface-conjugated synthetic nanoparticles (Nat Med, 2010, 16:1035-1041)

報告日期: 2010/12/21
報告時間: 17:10/18:00
報告學生: 李映瑩
講評老師: 吳炳慶

Full text:

Therapeutic cell engineering with surface-conjugated synthetic nanoparticles
Matthias T Stephan et al., Nature Medicine 16 (9), 1035-1042, 2010
Date: 2010/12/21 17:10~18:00
Presenter: Ying-ying Lee
Commentator: Ping-Ching Wu Ph. D.
Cancer immunotherapy use a variety of reagents and adjuvant drugs to stimulate the immune system to boosts available donor cells to destroy cancer cells1,2. Current obstacles in clinical treatment are dose-limiting toxicities of drugs usage and technical challenges of efficient gene transfer3,4. To overcome these challenges, this study employed adjuvant drug-loaded nanoparticles to develop a new donor-cell carrier to obtain cancer cell therapy effectively. Authors’ in-vitro result showed that their synthetic drug-carrier nanoparticles can sufficiently couple to the surface of therapeutic T cells. These nanoparticle- decorated T-cells not only retained cellular function but also had a capability to recognize antigen-expressing tumor cells. In authors’ in-vivo study, they used cytokines-encapsulated therapeutic T cells and inject into mice and showed their modified T-cells could release active cytokines to inhibit tumor growth and generate memory lymphocytes in lymph nodes and spleen. Finally, authors presented that TWS119 (a glycogen synthase kinase-3 inhibitor)-loaded therapeutic T-cells could enhanced the in vivo repopulation rate of hematopoietic stem cell. In conclusion, these drug-loaded particles could directly conjugate to the donor cells and markedly increased their therapeutic impact. These therapeutic T cells were promised vectors to fight diseases for actively targeted drug delivery.
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2.   Mackinnon, S. et al. Adoptive cellular therapy for cytomegalovirus infection following allogeneic stem cell transplantation using virus-specific T cells. Blood Cells Mol. Dis. 40, 63–67(2008).
3.   Berger, C. et al. Safety and immunological effects of IL-15 administration in nonhuman primates. Blood 114, 2417–2426 (2009).
4.   Thompson, J.A. et al. Recombinant interleukin 2 toxicity, pharmacokinetics and immunomodulatory effects in a phase I trial. Cancer Res. 47, 4202–4207(1987).