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
附件下載:

Full text: http://basicmed.med.ncku.edu.tw/admin/up_img/991221-3.pdf

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.
 
Reference
1.   Morgan, R.A. et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 314, 126–129 (2006).
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).