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Engineering anti‐GD2 monoclonal antibodies for cancer immunotherapy
Author(s) -
Ahmed Mahiuddin,
Cheung Nai-Kong V.
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.11.030
Subject(s) - medicine , neuroblastoma , cancer research , antibody , immunotherapy , immunoconjugate , monoclonal antibody , sarcoma , immunotoxin , cancer , chimeric antigen receptor , cancer immunotherapy , immunology , pathology , biology , genetics , cell culture
Ganglioside GD2 is highly expressed on neuroectoderm‐derived tumors and sarcomas, including neuroblastoma, retinoblastoma, melanoma, small cell lung cancer, brain tumors, osteosarcoma, rhabdomyosarcoma, Ewing's sarcoma in children and adolescents, as well as liposarcoma, fibrosarcoma, leiomyosarcoma and other soft tissue sarcomas in adults. Since GD2 expression in normal tissues is restricted to the brain, which is inaccessible to circulating antibodies, and in selected peripheral nerves and melanocytes, it was deemed a suitable target for systemic tumor immunotherapy. Anti‐GD2 antibodies have been actively tested in clinical trials for neuroblastoma for over the past two decades, with proven safety and efficacy. The main limitations have been acute pain toxicity associated with GD2 expression on peripheral nerve fibers and the inability of antibodies to treat bulky tumor. Several strategies have been developed to reduce pain toxicity, including bypassing complement activation, using blocking antibodies, or targeting of O‐acetyl‐GD2 derivative that is not expressed on peripheral nerves. To enhance anti‐tumor efficacy, anti‐GD2 monoclonal antibodies and fragments have been engineered into immunocytokines, immunotoxins, antibody drug conjugates, radiolabeled antibodies, targeted nanoparticles, T‐cell engaging bispecific antibodies, and chimeric antigen receptors. The challenges of these approaches will be reviewed to build a perspective for next generation anti‐GD2 therapeutics in cancer therapy.