We have located links that may give you full text access.
4-1BB and CD28 signaling plays a synergistic role in redirecting umbilical cord blood T cells against B-cell malignancies.
Human Gene Therapy 2010 January
Umbilical cord blood (UCB) T cells can be redirected to kill leukemia and lymphoma cells by engineering with a single-chain chimeric antigen receptor (CAR) and thus may have general applications in adoptive cell therapy. However, the role of costimulatory molecules in UCB T-cell activation and effector functions in context with CAR remains elusive. To investigate the effect of costimulatory molecules (4-1BB and CD28) on UCB T cells, we transduced UCB T cells with lentiviral vectors expressing Green Fluorescent Protein (GFP) and CAR for CD19 containing an intracellular domain of the CD3zeta chain and either a 4-1BB (UCB-19BBzeta) or a CD28 intracellular domain (UCB-1928zeta), both (UCB-1928BBzeta), or neither (UCB-19zeta). We found that UCB-19BBzeta and UCB-28BBzeta T cells exhibited more cytotoxicity to CD19(+) leukemia and lymphoma cell lines than UCB-19zeta and UCB-1928zeta, although differences in secretion of interleukin-2 and interferon-gamma by these T cells were not evident. In vivo adoptive transfer of these T cells into intraperitoneal tumor-bearing mice demonstrated that UCB-19BBzeta and UCB-1928BBzeta T cells mounted the most potent antitumor response. The mice adoptively transferred with UCB-1928BBzeta cells survived longer than the mice with UCB-19BBzeta. Moreover, UCB-1928BBzeta T cells mounted a more robust antitumor response than UCB-19BBzeta in a systemic tumor model. Our data suggest a synergistic role of 4-1BB and CD28 costimulation in engineering antileukemia UCB effector cells and implicate a design for redirected UCB T-cell therapy for refractory leukemia.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app