题名：Tumor antigen-specific T-cell expansion is greatly facilitated by in vivo priming.
作者：Dang Y, Knutson KL, Goodell V, dela Rosa C, Salazar LG, Higgins D, Childs J, Disis ML. Related Articles, Links
来源：Clin Cancer Res[IF=5.715]. 2007 Mar 15;13(6):1883-91.
摘要： Yushe Dang1, Keith L. Knutson1, Vivian Goodell1, Corazon dela Rosa1, Lupe G. Salazar1, Doreen Higgins1, Jennifer Childs1 and Mary L. Disis1,2
1 Tumor Vaccine Group, Center for Translational Medicine in Women s Health, University of Washington, and 2 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
Requests for reprints: Yushe Dang, Tumor Vaccine Group, Center for Translational Medicine in Women s Health, University of Washington, 815 Mercer Street, Box 358050, Seattle, WA 98109. Phone: 206-616-8447; Fax: 206-685-3128; E-mail: firstname.lastname@example.org.
Purpose: Adoptive T-cell therapy is a promising strategy for the treatment of patients with established tumors but is often limited to specific cancers where tumor-infiltrating lymphocytes, the source of T cells for ex vivo culture, can be obtained. In this study, we evaluated the feasibility of expanding HER-2/neuCspecific T cells derived from peripheral blood ex vivo following in vivo priming with a HER-2/neu peptide vaccine.
Experimental Design: Peripheral blood mononuclear cells from cytomegalovirus (CMV)Cseronegative and CMV-seropositive donors as well as HER-2/neuCpositive cancer patients who had or had not been vaccinated with a HER-2/neu peptideCbased vaccine was used as a source of T lymphocytes. Antigen-specific T-cell lines were generated by in vitro stimulation with antigen followed by nonspecific expansion on CD3/CD28 beads. The ability to expand antigen-specific T cells was assessed using IFN- and granzyme B enzyme-linked immunosorbent spot. The phenotype of the resultant T-cell lines was evaluated by flow cytometry, including the presence of FOXP3-expressing CD4+ T cells.
Results: The frequencies of CMV-specific T cells generated from CMV+ donors were >11-fold higher than the frequencies from CMVC donors (P = 0.001), with 22-fold increase of total number of CD3+ T cells. The frequencies of HER-2/neuCspecific T cells generated from the primed patients were >25-fold higher than the frequencies from unvaccinated patients (P = 0.006), with an average of a 19-fold increase of total number of CD3+ T cells. Using peripheral blood as the source of T cells did not result in concurrent expansion of FOXP3+CD4+ regulatory T cells despite the use of interleukin-2 in in vitro culture. Both CD4+ and CD8+ HER-2/neuCspecific T cells could be expanded. The extent of ex vivo expansion correlated with the magnitude of immunity achieved during immunization (P = 0.008).
Conclusion: Tumor-specific T cells can be efficiently expanded from the peripheral blood ex vivo following in vivo priming with a vaccine. This approach provides an effective method to generate tumor-specific polyclonal T cells for therapeutic use that could be applied to cancer patients with any tumor type. 6: