Characterization of an antitumor immune response after light-activated drug therapy using talaporfin sodium in a spontaneously metastasizing mammary tumor model

Abstract

3052 Background: An innovative light-activated drug therapy (Litx) is a cytoreductive treatment that uses light-emitting diodes to activate talaporfin sodium (LS11), a water-soluble drug, resulting in the production of singlet oxygen. Tumor destruction involves direct and indirect tumor kill through apoptosis, vascular occlusion, and potentially antitumor immunologic effects. To provide evidence for the potential antitumor immunologic effects, we have used the therapy to treat primary tumors and examine prevention of metastases in the 4T1 tumor model, an aggressive, spontaneously metastasizing murine mammary tumor model that mirrors human breast cancer. When grown in the mammary fat pad of BALB/c mice, untreated 4T1 tumors rapidly metastasize to lung, liver, lymph nodes, and brain. Methods: To confirm tumor kill by this therapy, the primary 4T1 tumors grown in mice were treated and animal survival was followed. To determine whether the therapy could enhance antitumor immunity and reduce metastases, the lymph node (LN) cells from treated and control mice were transferred to naïve recipient mice. Recipients were challenged with a tumorigenic dose of 4T1 cells 3 days after adoptive transfer and primary and secondary tumor growth in the recipients was examined. Results: Treatment of primary tumors significantly increased survival (p≤0.01) when compared to animals treated with either light or drug alone. LN cells isolated from treated mice, but not control mice, significantly inhibited primary tumor growth in recipients (p≤0.0001) and dramatically reduced the number of lung metastases present 40d after tumor challenge (p≤0.02). The ability to inhibit primary and secondary tumor growth in recipients depended on the presence of CD8+ T cells; depletion of CD8+ T cells from the LN abolished the effect. Preliminary evidence for such effect on untreated tumors has been observed in human trials of this therapy. Conclusions: These results indicated that this light-activated drug therapy not only destroyed the treated tumors directly but also controlled growth of untreated tumors through induction of a specific host antitumor immune response mediated by CD8+ T cells. [Table: see text]