Synergism of Epidermal Growth Factor Receptor–Targeted Immunotherapy With Photodynamic Treatment of Ovarian Cancer In Vivo

Abstract

A mechanistically nonoverlapping combination modality consisting of receptor tyrosine kinase inhibition with C225 and BPD-PDT is well tolerated, effective, and synergistic in mice.

Photochemically stimulated drug delivery increases the cytotoxicity and specificity of EGF–saporin

“…Increased cytotoxicity is reported after dual therapy with PDT and different chemotherapeutic drugs such as cisplatin (Nonaka et al 2002) cyclophosphamide (Casas et al 1998), 5-fluoro-2-deoxyuridine (5FdUr) (Zimmermann et al 2003), metotrexate and doxorubicin (Kirveliene et al 2006). Recently, novel anticancer drugs as TKIs (Dimitroff et al 1999, Liu et al 2007, mAbs (del Carmen et al 2005, Ferrario & Gomer 2006 and COX-2 inhibitors (Ferrario et al 2005) have been reported to enhance PDT-mediated toxicity. However, antagonistic responses have also been reported with PDT in combination with doxorubicin and 5FdUr (Zimmermann et al 2003, Kirveliene et al 2006.…”

“…However, antagonistic responses have also been reported with PDT in combination with doxorubicin and 5FdUr (Zimmermann et al 2003, Kirveliene et al 2006. Multimodality therapy is generally considered most effective when the different monotherapies have distinct mechanisms of action (del Carmen et al 2005, Zhang et al 2005, Soffietti et al 2007). …”

Selective treatment and monitoring of disseminated cancer micrometastases in vivo using dual-function, activatable immunoconjugates

“…To address the challenges associated with treating and detecting occult, residual, and drug-resistant micrometastases before gross recurrence, it is necessary to develop (i) targeted treatments with high tumor selectivity and distinct mechanisms of cell death (12)(13)(14) to overcome dose-limiting toxicities and chemoresistance; and (ii) high-resolution approaches with sufficient contrast to monitor microscopic disease. Here, we address both of these needs by developing an activatable construct targeted to markers overexpressed by cancer cells with dual functionality for both therapy and imaging, and integrate this into a quantitative fluorescence microendoscopy platform for longitudinal monitoring of micrometastases.…”

The role of photodynamic therapy (PDT) physics

“…C225, a monoclonal antibody that inhibits the receptor tyrosine kinase activity of EGFR, has been shown to enhance the PDT treatment in ovarian cancer. 94,95 Other combined modalities seek to target treatment-induced angiogenesis and/or inflammation to enhance the effectiveness of PDT. 96 …”