A New Class, Now in Session: the First HLA Class II Restricted T Cell Receptor that Recognizes the Cancer Testis Antigen, MAGE-A3, Developed for Cancer ImmunotherapyNIH scientists have developed T cell receptors (TCRs) against the melanoma antigen family A3 (MAGE-A3) tumor antigen in the context of major histocompatibility complex (MHC) class II molecule HLA-DP-beta1*04. They are the first HLA class II restricted MAGE-A3 TCRs developed for use in adoptive immunotherapy. Previously developed MAGE-A3 TCRs are HLA class I restricted and generate CD8+ T cell responses to mediate tumor regression in some patients with MAGE-A3+ tumors. Other patients may not respond due to a lack of CD4+ T cells participation. Cancer immunotherapy with these new HLA class II TCRs could yield a robust and effective CD4+ T cell immune response that selectively targets MAGE-A3 expressing tumors without generating toxicity against healthy cells.
MAGE-A3 is a cancer testis antigen expressed on many types of cancer cells that blocks the functions of tumor suppressor proteins to mediate tumor growth and spreading. MAGE-A3 is not expressed on normal cells other than non-MHC expressing germ cells of the testis, which do not generate an immune response. Thus, MAGE-A3 represents an ideal target for cancer immunotherapies that are predicted to generate fewer toxic side effects than current standard cancer treatments.
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