Constructs targeting afp peptide/mhc complexes and uses thereof

Abstract

The present application provides constructs comprising an antibody moiety that specifically binds to a complex comprising an AFP peptide and an MHC class I protein. Also provided are methods of making and using these constructs.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application No. 62 / 142,958, filed on Apr. 3, 2015, U.S. Provisional Application No. 62 / 244,653, filed on Oct. 21, 2015, and U.S. Provisional Application No. 62 / 304,915, filed on Mar. 7, 2016, all of which are hereby incorporated by reference in their entireties.FIELD OF THE INVENTION[0002]This invention pertains to antibody constructs that specifically bind MHC molecules complexed with AFP peptides, and uses thereof including treating and diagnosing diseases.SUBMISSION OF SEQUENCE LISTING ON ASCII TEXT FILE[0003]The content of the following submission on ASCII text file is incorporated herein by reference in its entirety: a computer readable form (CRF) of the Sequence Listing (file name: 750042000140SEQLIST.txt, date recorded: Apr. 1, 2016, size: 65 KB).BACKGROUND OF THE INVENTION[0004]Cell surface proteins constitute only a small fraction of the cellular proteins and these proteins are...

AI Technical Summary

Benefits of technology

The patent text describes an anti-AMC construct that specifically binds to a complex of an AFP peptide and an MHC class I protein. The anti-AMC construct can be an isolated antibody moiety that cross-reacts with a different MHC class I protein or an interspecies variant of the AFP peptide. The anti-AMC construct can be a full-length antibody, a Fab, a Fab', a (Fab')2, an Fv, or a single chain Fv (scFv). The anti-AMC construct has a high affinity for the complex and can be used to detect and target cells that express the complex.

Problems solved by technology

However, because AFP is not a cell-surface protein, targeting AFP has not been a very active area for anti-cancer antibody drug development.

Non-surgical treatments, such as trans-arterial chemoembolization (TACE / TAE), radio-frequency ablation and systemic targeted agent like sorafenib, have been shown to reduce tumor burden and improve survival rate but these treatments do not eradicate cancer cells and the patients frequently relapse.

Antibodies directed against the AFP protein have little therapeutic efficacy since AFP is not a cell-surface protein, and may be present at high circulating levels, thus reducing any specific targeting of the antibody to the cells expressing AFP.

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