Targeting O-Acetyl-GD2 Ganglioside for Cancer Immunotherapy
نویسندگان
چکیده
Target selection is a key feature in cancer immunotherapy, a promising field in cancer research. In this respect, gangliosides, a broad family of structurally related glycolipids, were suggested as potential targets for cancer immunotherapy based on their higher abundance in tumors when compared with the matched normal tissues. GD2 is the first ganglioside proven to be an effective target antigen for cancer immunotherapy with the regulatory approval of dinutuximab, a chimeric anti-GD2 therapeutic antibody. Although the therapeutic efficacy of anti-GD2 monoclonal antibodies is well documented, neuropathic pain may limit its application. O-Acetyl-GD2, the O-acetylated-derivative of GD2, has recently received attention as novel antigen to target GD2-positive cancers. The present paper examines the role of O-acetyl-GD2 in tumor biology as well as the available preclinical data of anti-O-acetyl-GD2 monoclonal antibodies. A discussion on the relevance of O-acetyl-GD2 in chimeric antigen receptor T cell therapy development is also included.
منابع مشابه
O-acetylated gangliosides: Structure, biosynthesis, immunogenicity, functions and their potential for cancer immunotherapy
Sialic acid O-acetylation is a developmentally regulated modification of gangliosides implicated in ontogeny and tumor progression. Their existence has been underestimated in the past because of their alkali-labile nature and their transient expression. New data indicates, however, that O-acetylated gangliosides perform important function in tumor malignancy. Best studied O-acetyl-GD3 blocks th...
متن کاملKinetic and spatial interrelationships between ganglioside glycosyltransferases and O-acetyltransferase(s) in human melanoma cells.
The melanoma-associated disialogangliosides 9(7)-O-acetyl-GD3 and 9(7)-O-acetyl-GD2 have been structurally well characterized. However, the compartmentalization and sequence of action of the biosynthetic activities responsible for synthesizing these molecules remain obscure. Here, we have studied the spatial and temporal interrelationships among the activities responsible for the later stages o...
متن کاملTargeting and killing glioblastoma with monoclonal antibody to O-acetyl GD2 ganglioside
There are still unmet medical needs in the treatment of glioblastoma, the most common and the most aggressive glioma of all brain tumors. Here, we found that O-acetyl GD2 is expressed in surgically resected human glioblastoma tissue. In addition, we demonstrated that 8B6 monoclonal antibody specific for O-acetylat GD2 could effectively inhibit glioblastoma cell proliferation in vitro and in viv...
متن کاملA Monoclonal Antibody to O-Acetyl-GD2 Ganglioside and Not to GD2 Shows Potent Anti-Tumor Activity without Peripheral Nervous System Cross-Reactivity
BACKGROUND Monoclonal antibodies (mAb) against GD2 ganglioside have been shown to be effective for the treatment of neuroblastoma. Beneficial actions are, however, associated with generalized pain due to the binding of anti- GD2 mAbs to peripheral nerve fibers followed by complement activation. Neuroblastoma cells that express GD2 also express its O-acetyl derivative, O-acetyl- GD2 ganglioside ...
متن کاملAnti-GD2/4-1BB chimeric antigen receptor T cell therapy for the treatment of Chinese melanoma patients
BACKGROUND Chimeric antigen receptor (CAR)-engineered T cells have demonstrated promising clinical efficacy in patients with B cell lymphoma. However, the application of CAR-T cell therapy in the treatment of other solid tumors has been limited. We incorporated 4-1BB into the anti-GD2 CAR-T cells to test their cytotoxicity in melanoma in vitro and in vivo. Moreover, we reported the expression o...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
دوره 2017 شماره
صفحات -
تاریخ انتشار 2017