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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.

Development Status:
  • Early-stage
  • Pre-clinical
  • In vitro data available

Steven A Rosenberg (NCI)
Paul F Robbins (NCI)
Xin Yao (NCI)

Patent Status:
HHS, Reference No. E-230-2012/0
US, Application No. 61/701,056 filed 14 Sep 2012

Related Technologies:
US, Application No. 61/405,668 filed 22 Oct 2010, Reference No. E-236-2010/0
PCT, Application No. PCT/US2011/57272 filed 22 Oct 2011, Reference No. E-236-2010/0
US, Application No. 61/535,086 filed 15 Sep 2011, Reference No. E-266-2011/0
PCT, Application No. PCT/US2012/054623 filed 11 Sep 2012, Reference No. E-266-2011/0

For Licensing Information Please Contact:
Samuel Bish Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Phone: 301-435-5282
Fax: 301-402-0220

Ref No: 2497

Updated: 11/2012

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