Abrogation of TNFalpha; production is crucial for suppressing side effects due to systemic expression of IL-12 in cancer immunotherapy

BIBIANA BARRIOS; NATALIA S. BAEZ; DELLA REYNOLDS; PABLO IRIBARREN; HOWARD A. YOUNG; MARIA CECILIA RODRIGUEZ-GALAN

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2014 p. 1 - 1

1932-6203

ince more than a decade ago, the cytokine IL-12 has been utilized alone or in combination with other drugs, as a treatment in cancer patients. The numerous anti-tumor properties of IL-12 still generate interest in the use of this cytokine even though it has demonstrated toxicity when administrated systemically. As an approach to overcome this toxicity, numerous laboratories have attempted to induce IL-12 expression at the site of the tumor, however; for tumors difficult to remove surgically or in the case of disseminated metastasis, systemic expression of this cytokine still remains as the most efficient method of administration. Nevertheless, finding alternatives in the use of IL-12 in the treatment of cancer and also unraveling the causes of IL-12-side effects remain a challenge. In the present work we demonstrate that systemic expression of IL-12 through hydrodynamic injection of IL-12 cDNA is able to induce different types of liver lesions associated with pathology. Hepatic toxici