Neoadjuvant intratumoral cytokine-loaded microspheres are superior to postoperative autologous cellular vaccines in generating systemic anti-tumor immunity
Arora, Alisha; Su, Gang; Mathiowitz, Edith; Reineke, Joshua; Chang, Alfred E.; Sabel, Michael S.
2006-10-01
Citation
Arora, Alisha; Su, Gang; Mathiowitz, Edith; Reineke, Joshua; Chang, Alfred E.; Sabel, Michael S. (2006). "Neoadjuvant intratumoral cytokine-loaded microspheres are superior to postoperative autologous cellular vaccines in generating systemic anti-tumor immunity." Journal of Surgical Oncology 94(5): 403-412. <http://hdl.handle.net/2027.42/55822>
Abstract
Background Sustained intratumoral cytokine release using poly-lactic acid microspheres (PLAMs) can induce a systemic immune response, shifting immunotherapy to the neoadjuvant setting. Methods C57BL6 mice with established B16 melanomas underwent a single intralesional injection of IL-12, TNF-Α or GM-CSF PLAM, alone or in combination. Tumor draining lymph nodes (TDLN) and spleens were assessed for a specific anti-tumor response by IFNΓ release assay and ELISPOT. Results Intralesional injection of TNF-Α, alone or in combination, resulted in significant tumor ablation. The induction of tumor specific reactive T-cells in the TDLN was greatest with IL-12 and TNF-Α. Only mice treated with IL-12 and TNF-Α demonstrated a substantial T-cell response in cultured splenocytes. This combination resulted in a significant reduction in new tumors after re-challenge. Adjuvant therapy, using irradiated B16 cells in combination with equivalent doses of IL-12 and TNF-Α, failed to generate a similar T-cell response or prevent re-challenge. Conclusions Intratumoral IL-12 and TNF-Α loaded PLAM leads to both local eradication of tumor and the induction of specific anti-tumor T-cells in the lymph nodes and spleens, resulting in memory immune response. Neoadjuvant treatment was significantly superior to postoperative autologous cellular vaccines using IL-12 and TNF-Α PLAM. J. Surg. Oncol. 2006;94:403–412. © 2006 Wiley-Liss, Inc.Publisher
Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-4790 1096-9098
Other DOIs
PMID
16967445
Types
Article
URI
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16967445&dopt=citationMetadata
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