Immunotherapy in Nonmelanoma Skin Cancer
Immunotherapy in Nonmelanoma Skin Cancer
mAbs aim at specific antigens associated with tumor cells residing on the surface of the cell. Antitumor antibodies can be effective against tumors by different mechanisms including cell-mediated cytoxicity, opsonization followed by phagocytosis and activation of complement, and finally, blockade of immunosuppressant molecules. The most important point in this field is the need to find certain pathways with a significant role in the process of tumorigenesis, which can be targeted by mAbs. Although mAbs are widely used in different cancer types, there are few records of their application in NMSC therapy, so there are insufficient data for comparison of this modality with other modalities.
Overexpression of the EGF receptor has been observed in SCCHN. This leads to increased cell survival due to constitutive activation of intracellular tyrosine kinase. Cetuximab, a human–murine chimeric mAb against the EGF receptor, has received US FDA approval for use in localized SCCHN in combination with radiation, as well as monotherapy in chemotherapy-resistant recurrent or metastatic SCCHN.
Two fully human mAbs to the EGF receptor, zalutumumab and panitumumab, are currently under investigation in clinical trials.
VEGF has a significant role in angiogenesis and can be secreted from tumor cells in response to hypoxia. Antibodies against VEGF have been used in the treatment of different cancers and clinical trials of their usage in SCCHN are ongoing.
It has been demonstrated that anti-CTLA-4 has a preventive role in the development of UV-induced tumors. In addition, anti-CTLA-4 treatment has induced long-term protective immunity in mice. As CTLA-4 inhibition hinders the suppressor activity of UV-induced CD4CD25 T cells, it has been postulated that reduced photocarcinogenesis can be a result of decreased numbers or function of suppressor T cells. Two CTLA-4 antibodies, ipilimumab and tremelimumab, have been used successfully in the treatment of melanoma. However, there are no available data regarding the role of these drugs in the treatment of NMSC. As interfering with CTLA-4 signaling intensifies antitumor immunity by inhibiting UV-induced immunosuppression, it could be a promising treatment for NMSC as well.
mAbs Have Been Developed for NMSC Treatment
mAbs aim at specific antigens associated with tumor cells residing on the surface of the cell. Antitumor antibodies can be effective against tumors by different mechanisms including cell-mediated cytoxicity, opsonization followed by phagocytosis and activation of complement, and finally, blockade of immunosuppressant molecules. The most important point in this field is the need to find certain pathways with a significant role in the process of tumorigenesis, which can be targeted by mAbs. Although mAbs are widely used in different cancer types, there are few records of their application in NMSC therapy, so there are insufficient data for comparison of this modality with other modalities.
EGF Receptor Inhibitors
Overexpression of the EGF receptor has been observed in SCCHN. This leads to increased cell survival due to constitutive activation of intracellular tyrosine kinase. Cetuximab, a human–murine chimeric mAb against the EGF receptor, has received US FDA approval for use in localized SCCHN in combination with radiation, as well as monotherapy in chemotherapy-resistant recurrent or metastatic SCCHN.
Two fully human mAbs to the EGF receptor, zalutumumab and panitumumab, are currently under investigation in clinical trials.
VEGF Inhibitors
VEGF has a significant role in angiogenesis and can be secreted from tumor cells in response to hypoxia. Antibodies against VEGF have been used in the treatment of different cancers and clinical trials of their usage in SCCHN are ongoing.
Anti-CTLA-4 Antibody
It has been demonstrated that anti-CTLA-4 has a preventive role in the development of UV-induced tumors. In addition, anti-CTLA-4 treatment has induced long-term protective immunity in mice. As CTLA-4 inhibition hinders the suppressor activity of UV-induced CD4CD25 T cells, it has been postulated that reduced photocarcinogenesis can be a result of decreased numbers or function of suppressor T cells. Two CTLA-4 antibodies, ipilimumab and tremelimumab, have been used successfully in the treatment of melanoma. However, there are no available data regarding the role of these drugs in the treatment of NMSC. As interfering with CTLA-4 signaling intensifies antitumor immunity by inhibiting UV-induced immunosuppression, it could be a promising treatment for NMSC as well.