Neoadjuvant immunotherapy with the combination of intratumoral IL-12 and TNF-α encapsulated
in poly-lactic acid microspheres (PLAM) generate a greater systemic immune response
than either cytokine alone. We sought to examine the effector cells responsible for
this synergy using the poorly immunogenic B16 melanoma and MCA205 sarcoma cell lines.
Splenocytes from MCA205 bearing mice treated with IL-12 and TNF-α PLAM contained significantly
more tumor-specific IFN-γ secreting cells than IL-12 alone. Adoptive transfer of lymphocytes
from mice treated by the combination mediated significant tumor regression in mice
bearing established pulmonary metastases. In mice bearing bilateral tumors, treatment
of the primary with IL-12 and TNF-α PLAM, resulted in suppression of contralateral
tumor growth. Both the local and distant effects were absent in mice depleted of CD8+
T-cells. In B16 bearing mice with established pulmonary disease, only the combination
of intratumoral IL-12 and TNF-α resulted in a significant reduction of lung nodules.
Both the local and distant effects were eradicated in mice depleted of either CD8+
T-cells or NK cells. The local and sustained release of IL-12 and TNF-α using PLAM
synergistically activate both a cytotoxic T-cell and NK cell response, although their
impact varies with MHC class I expression.
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Article info
Publication history
Accepted:
May 5,
2007
Footnotes
Funded in part by NIH Grant CA102602-01 and a grant from the Gillson-Longenbaugh Foundation.
Identification
Copyright
© 2007 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
