Intratumoral IL-12 and TNF-α–Loaded Microspheres Lead To Regression of Breast Cancer and Systemic Antitumor Immunity

Abstract

A single intratumoral injection of IL-12 and TNF-alpha-loaded PLAM into a breast tumor leads to infiltration by polymorphonuclear cells and CD8+ T-cells with subsequent tumor regression. In addition, this local therapy induces specific antitumor T-cells in the lymph nodes and spleens, resulting in memory immune response.

New insights into IL-12-mediated tumor suppression

“…injection of biodegradable polylactic miscrospheres loaded with IL-12 alone 90 or in combination with TNF-a, IL-18 or GM-CSF. [91][92][93] An effective strategy for treating malignant glioma was described by Sonabend et al, 94 using modified polyethylenimine complexes as vehicles for IL-12 gene therapy. Of note, the synergy resulting from combining this treatment with chemotherapy resulted in 100% survival of treated mice.…”

Neoadjuvant intratumoral cytokine‐loaded microspheres are superior to postoperative autologous cellular vaccines in generating systemic anti‐tumor immunity

“…In this way, the tumor itself serves as the vaccine, precluding the cost and difficulty in establishing a cell line and transfecting it with the gene for a cytokine. We have previously described an alternate strategy for in situ cytokine delivery: the use of slowrelease polymer microspheres [1,12,13]. Using the poorly immunogenic B16 (murine melanoma) model, we sought to identify the optimum cytokines (or combination) for in situ vaccination, and to compare this neoadjuvant approach to the adjuvant use of autologous cellular vaccines.…”

“…Our results confirm that the combination of IL-12 and TNF-a appears to be a particularly effective combination. Synergistic effects possibly include skewing towards a Th1 response [24], induction of the tumoricidal activity of macrophages [25], and increased necrosis and tumor infiltration of both PMN and CD8þ cells at the site of the tumor [13].…”

Biodegradable polymers suitable for tissue engineering and drug delivery systems

“…So, it was shown that PLA loaded microspheres with intratumoral interleukin 12 (IL-12), tumour necrosis factor (TNF), and granulocyte-macrophage colony stimulating factor (GM-CSF) have produced antitumor response in a murine model of breast cancer [86]. Similarly, paclitaxel-encapsulated PLGA microspheres significantly inhibited lung tumour growth in vivo [87], and antigen CA125 loading in PLGA microspheres showed significant T-cell proliferation in vitro as well as promising response during ovarian cancer therapy [88].…”