Metastatic disease is the major cause of morbidity and mortality in
cancer. Although surgery,
chemotherapy, or radiation can often control primary
tumor growth, successful eradication of disseminated
metastases remains rare. We have now tested whether direct targeting
tumor tissues to generate antitumor immune response before surgical excision produces sufficient CTL against
micrometastases. One unsolved problem is whether such response allows coming CTL to be educated and then exit the
tumor site. Another unsolved problem is whether these CTL can then patrol and effectively eliminate spontaneously metastasized
tumor cells in the periphery. In this study, we have shown that adenovirus-expressing TNFSF14 [LIGHT (name derived from homologous to lymphotoxins, shows inducible expression, and competes with herpes simplex virus
glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes); Ad-LIGHT] inoculated directly into primary 4T1
tumor, a highly aggressive, spontaneously metastasizing mammary
carcinoma, followed by surgical removal of the primary
tumor can eradicate established and disseminated metastatic
tumor cells in the peripheral tissues. Furthermore, we clearly show with a
fibrosarcoma model Ag104L(d) that local treatment can generate plenty of
tumor-specific CTL that exit the primary
tumor and infiltrate distal
tumors to completely eradicate distal
tumors. Therefore, targeting the primary
tumor with Ad-LIGHT before surgical excision is a new strategy to elicit better immune response for the eradication of spontaneous
metastases.