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Neoadjuvant intratumoral cytokine‐loaded microspheres are superior to postoperative autologous cellular vaccines in generating systemic anti‐tumor immunity
Author(s) -
Arora Alisha,
Su Gang,
Mathiowitz Edith,
Reineke Joshua,
Chang Alfred E.,
Sabel Michael S.
Publication year - 2006
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.20572
Subject(s) - elispot , medicine , tumor necrosis factor alpha , immune system , cytokine , immunotherapy , lymph , adjuvant , splenocyte , lymph node , neoadjuvant therapy , cellular immunity , cancer research , immunology , t cell , pathology , cancer , breast cancer
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.