1 research outputs found
Broad-spectrum Anti-tumor and Anti-metastatic DNA Vaccine Based on p62- encoding Vector
Abstract
Autophagy plays an important role in neoplastic transformation of cells and in resistance of
cancer cells to radio and chemotherapy. p62 (SQSTM1) is a key component of autophagic
machinery which is also involved in signal transduction. Although recent empirical observations
demonstrated that p62 is overexpressed in variety of human tumors, a mechanism of p62
overexpression is not known. Here we report that the transformation of normal human mammary
epithelial cells with diverse oncogenes (RAS, PIK3CA and Her2) causes marked accumulation
of p62. Based on this result, we hypothesized that p62 may be a feasible candidate to be an anti-
cancer DNA vaccine. Here we performed a preclinical study of a novel DNA vaccine encoding
p62. Intramuscularly administered p62-encoding plasmid induced anti-p62 antibodies and
exhibited strong antitumor activity in three models of allogeneic mouse tumors – B16 melanoma,
Lewis lung carcinoma (LLC), and S37 sarcoma. P62-encoding plasmid has demonstrated its
potency both as a preventive and therapeutic vaccine. Importantly, p62 vaccination drastically
suppressed metastasis formation: in B16 melanoma where tumor cells where injected
intravenously, and in LLC and S37 sarcoma with spontaneous metastasis. Overall, we conclude
that a p62-encoding vector(s) constitute(s) a novel, effective broad-spectrum antitumor and anti-
metastatic vaccine feasible for further development and clinical trials