Factor VII-Targeted Photodynamic Therapy for Breast Cancer and Its Therapeutic Potential for Other Solid Cancers and Leukemia

Overcome the Impairment of NK Cells for Icon and Antibody Immunotherapy of Cancer

“…In the past decades, effects have been focused on identi-fication of target antigens on one of two major tumor compartments, either tumor cells or tumor neovasculature, and subsequently several therapeutic chimeric or completely humanized antibodies have been developed against common growth factors or their receptors [6], such as epidermal growth factors HER-1 (Cetuximab), HER-2/neu (Trastuzumab), or angiogenic growth factors, such as vascular endothelial growth factor (VEGF) (Bevacizumab), for cancer immunotherapy. We proposed that simultaneous targeting of both the tumor compartments, i.e., tumor cells and tumor neovasculature, could achieve better therapeutic effect than targeting of tumor cells or tumor neovasculature alone [7]. In this regard, we constructed in 1999 the first dual neovascular-and tumor cell-targeting antibody-like factor VII/IgG1 Fc immunoconjugate molecule [8], later called an Icon [9,10] (Figure 1).…”

Dual-Targeting of Tumor Cells and Tumor Neovasculature by Tissue Factor- Targeted Photodynamic Therapy

“…We [11][12][13][14] and several other groups [15,16] showed that tissue factor (TF) was selectively expressed by tumor angiogenic vascular endothelial cells and was also overexpressed by many types of cancer cells in melanoma, breast, lung and brain tumors. Thus we conclude that TF is a common yet specific biomarker and therapeutic target molecule for both the tumor cells and tumor neovasculature [10][11][12]17,18]. By choosing the receptor TF as a target molecule and using its natural ligand, coagulation factor VII (fVII), as a targeting vehicle, we have successfully developed a novel dtPDT, namely fVII-targeted PDT (fVII-tPDT) using fVII-SnCe6 (activation wavelength at 635 nm) or fVII-VP (activation wavelength at 689 nm) conjugates, for treatment of human breast [12,17,18] and lung cancer [11] and wet macular degeneration [19] in preclinical studies.…”

“…Since TF is expressed by tumor angiogenic vascular endothelial cells and by cancer cells of human solid cancers and leukemia [18], we believe that TF-targeted therapeutics by using fVII as targeting vehicle, including fVII-tPDT that we recently developed [10][11][12]17,18] and fVII/IgG1 Fc (Icon immunotherapy) that we previously developed [13,14,20,21] could have broad therapeutic potential for solid cancer and leukemia.…”

“…The bottleneck of development of such dtPDT is to identify a common yet specific biomarker on both tumor compartments [10]. We [11][12][13][14] and several other groups [15,16] showed that tissue factor (TF) was selectively expressed by tumor angiogenic vascular endothelial cells and was also overexpressed by many types of cancer cells in melanoma, breast, lung and brain tumors.…”

The future of immune checkpoint blockade immunotherapy: towards personalized therapy or towards combination therapy

“…The combination immunotherapy can target different molecules on some or all major tumor compartments, including but not limited to the cancer cells, tumor neovasculature, cancer stem cells, MDSC, Treg and TAM, or ideally, target the same molecule that is commonly expressed by these major tumor compartments. In this regard, we believe that tissue factor (also known as coagulation factor III or CD142) is one of few such promising and common target molecules as it is commonly yet selectively expressed on many types of solid cancer cells as well as leukemic cells (21,22), tumor angiogenic vascular endothelial cells in vitro (23) and in vivo (22,(24)(25)(26) and cancer stem cells (27).…”