Chimeric antigen receptor targeting sialyl lewis a and uses thereof

Abstract

The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., pancratic cancer). It relates to antigen recognizing receptor (e.g., chimeric antigen receptors (CARs)) that specifically target Sialyl Lewis A (e.g., human Sialyl Lewis A), and immunoresponsive cells comprising such CARs. The presently disclosed Sialyl Lewis A-specific CARs have enhanced immune-activating properties, including anti-tumor activity.

Description

[0001] Cross References to Related Applications [0002] This application claims priority from and claims priority to U.S. Provisional Application No. 62 / 748,198, filed October 19, 2018, the entire contents of which are incorporated herein by reference. technical field [0003] The presently disclosed subject matter provides methods and compositions for treating cancer, such as pancreatic cancer. It involves a chimeric antigen receptor (CAR) that specifically targets sialylated Lewis A. The presently disclosed subject matter also provides immune response cells comprising such CARs, and methods of using such CARs and such cells to treat cancer (eg, pancreatic cancer). Background technique [0004] Cell-based immunotherapy is a therapy with potential for cancer treatment. T cells and other immune cells can be modified to target tumors by introducing genetic material encoding artificial or synthetic receptors for antigens, known as chimeric antigen receptors (CARs), which ar...

AI Technical Summary

Problems solved by technology

Although all or most B-cell malignancies express CD19 (Brentjens et al., Nat Med (2003); 9:279-286), many potential CAR targets are expressed on only a small fraction of all tumor cells in a patient , causing the risk of antigen escape

Low levels of antigen expression may also lead to resistance to CAR therapy (Fry et al., Nat Med (2018); 24:20-28)

Targeting of two or more antigens can be performed in the case of defined escape populations or clones (Wilkie et al., J Clin Immunol (2012); 32:1059-1070; Kloss et al., Nat Biotechnol (2013); 31:71-75; Ruella et al., J Clin Invest (2016); 126:3814-3826; Hegde et al., J Clin Invest (2016); 126:3036-3052; Zah et al., Cancer Immunol Res 2016;4: 498-508), but other approaches are needed to overcome greater or uncertain target heterogeneity

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