A New Class, Now in Session: the First HLA Class II Restricted T Cell Receptor that Recognizes the Cancer Testis Antigen, MAGE-A
Posted Nov 15 2012 7:00pm
Description of Invention: NIH 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.
A personalized immunotherapy to mediate regression of many types of cancers using human T cells expressing a HLA class II TCR.
An adoptive immunotherapy combining T cells engineered to express a HLA class I restricted TCR with HLA class II TCR-expressing T cells to enhance the antitumor response by eliciting CD8+ and CD4+ T cell immune responses in patients.
A research tool to investigate signaling pathways in MAGE-A3 antigen expressing cancer cells.
An in vitro diagnostic tool to screen for cells expressing the MAGE-A3 tumor antigen.
Class I restricted TCRs can only treat a subset of patients, but since ~80% of patients express the HLA-DP-beta1*04 class II HLA allele, this TCR expands the population pool treatable with MAGE-A3 TCRs to include the majority of patients.
MAGE-A3 is a highly expressed tumor target on many cancer cells, so MAGE-A3 TCR therapy should be a viable treatment option for many cancer cases.
MAGE-A3 is only expressed on tumor cells and non-MHC expressing cells so these TCRs should target MAGE-A3 expressing tumor cells with little or no side effects/toxicity to normal cells.
For Licensing Information Please Contact: Samuel Bish Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: email@example.com Phone: 301-435-5282 Fax: 301-402-0220