Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 62, Issue 11, Pages 1649-1662Publisher
SPRINGER
DOI: 10.1007/s00262-013-1464-0
Keywords
Central memory T cells (Tcm); CD62L; Dendritic cells (DC); Intracranial cerebellar (IC) tumor; Adoptive cell transfer (ACT); Immunotherapy
Categories
Funding
- NIH [5P50-CA108786, 3R21CA132891-02S1, 5R01-CA135272-05, 5R21NS 067975-02, 5R21NS067980-02, 5R21NS068057-02, 3R01CA135272-02S1, R25-NS065731, 5P50-NS020023-29, 1P01-CA154291-01A1]
- Accelerate Brain Cancer Cure
- National Brain Tumor Society
- American Brain Tumor Association
- Pediatric Brain Tumor Foundation of the United States
- Goldhirsh Foundation
- Brain Tumor Society
- Ivy Foundation DTRI
- Duke University Biomarker Factory Duke Cancer Institute, Duke Chandran
Ask authors/readers for more resources
Adoptive cell transfer (ACT) using ex vivo-expanded anti-tumor T cells such as tumor-infiltrated lymphocytes or genetically engineered T cells potently eradicates established tumors. However, these two approaches possess obvious limitations. Therefore, we established a novel methodology using total tumor RNA (ttRNA) to prime dendritic cells (DC) as a platform for the ex vivo generation of anti-tumor T cells. We evaluated the antigen-specific expansion and recognition of T cells generated by the ttRNA-DC-T platform, and directly modulated the differentiation status of these ex vivo-expanded T cells with a cytokine cocktail. Furthermore, we evaluated the persistence and in vivo anti-tumor efficacy of these T cells through murine xenograft and syngeneic tumor models. During ex vivo culture, IL-2 preferentially expanded CD4 subset, while IL-7 enabled homeostatic proliferation from the original precursors. T cells tended to lose CD62L during ex vivo culture using IL-2; however, IL-12 could maintain high levels of CD62L by increasing expression on effector T cells (Tem). In addition, we validated that OVA RNA-DC only selectively expanded T cells in an antigen-specific manner. A cytokine cocktail excluding the use of IL-2 greatly increased CD62L(high) T cells which specifically recognized tumor cells, engrafted better in a xenograft model and exhibited superior anti-tumor activities in a syngeneic intracranial model. ACT using the ex vivo ttRNA-DC-T platform in conjunction with a cytokine cocktail generated potent CD62L(high) anti-tumor T cells and imposes a novel T cell-based therapeutic with the potential to treat brain tumors and other cancers.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available