High avidity antigen recognizing constructs
The present invention pertains to novel high avidity antigen recognizing constructs, such as antibodies or T cell receptors, which specifically bind to the melanoma associated antigen (MAGE) A1. The constructs of the invention are particularly useful for the diagnosis, prevention or therapy of tumorous diseases which are characterized by the specific expression of the MAGE-A1 antigen. Furthermore provided are nucleic acids, vectors and host cells—such as CD4 or CD8 positive T cells—which encode, comprise or present the antigen recognizing constructs of the invention. The invention thus provides new means for immune therapy, specifically adoptive T cell therapy, for treating cancer.
1. A T cell receptor (TCR), or derivative or fragment thereof, comprising:
a) an alpha chain comprising CDR sequences comprising amino acid sequences of SEQ ID NO: 40, 41, and 1; and a beta chain comprising CDR sequences comprising amino acid sequences of SEQ ID NO: 46, 47, and 4; or
b) an alpha chain comprising CDR sequences comprising amino acid sequences of SEQ ID NO: 42, 43, and 2; and a beta chain comprising CDR sequences comprising amino acid sequences of SEQ ID NO: 48, 49, and 5; or
c) an alpha chain comprising CDR sequences comprising amino acid sequences of SEQ ID NO: 44, 45, and 3; and a beta chain comprising CDR sequences comprising amino acid sequences of SEQ ID NO: 50, 51, and 6.
2. The TCR, or derivative or fragment thereof, according to claim 1 , wherein said TCR binds specifically to the MAGE-A1 antigen.
3. The TCR, or derivative or fragment thereof, according to claim 1 , wherein said TCR induces an immune response.
4. The TCR, or derivative or fragment thereof, according to claim 3 , wherein the immune response is characterized by an increase in interferon (IFN) γ levels.
5. The TCR, or derivative or fragment thereof, according to claim 1 , wherein said TCR is in the form of an αβ heterodimer.
6. The TCR, or derivative or fragment thereof, according to claim 1 , wherein said TCR is in a single chain format comprising said alpha chain and said beta chain.
7. The TCR, or derivative or fragment thereof, according to claim 6 , wherein said TCR is fused to a human cytokine.
8. The TCR, or derivative or fragment thereof, according to claim 7 , wherein said human cytokine is IL-2, IL-7 or IL-15.