Antibody blockade induces anticancer response in solid tumor models. First in vivo validation of KLRG1 as a cancer immunotherapy target. KLRG1 is a driver of adaptive resistance to immunotherapy in humans.
NEWTON, Mass., March 26, 2019 /PRNewswire/ — Abcuro, Inc., a biopharmaceutical company developing first-in-class immunomodulatory therapeutics, announced the publication of proof-of-concept data describing KLRG1 as a promising new target for cancer immunotherapy. The article, published in Oncotarget ( link ), reports the anticancer activity of KLRG1 antibody blockade in syngeneic mouse models of breast cancer, colon cancer and melanoma. The study also highlights the expression of KLRG1 in human tumor infiltrating lymphocytes (TILs) and its role in adaptive resistance to immunotherapies.
KLRG1 was identified as a critical immune inhibitory receptor by datamining expression profile databases with the aim of finding immune checkpoint receptors that align with the state of T cell differentiation. This analysis showed that KLRG1 is, genome wide, the immune inhibitory receptor that best aligns with degree of T cell differentiation. Compared to other clinical targets that are active in early and intermediate stages of T cell differentiation (such as CTLA-4 and PD-1), KLRG1 functions as the ultimate break on the most differentiated and cytotoxic T cells. Furthermore, KLRG1 expression on a differentiated subset of T cells and the high cytotoxic potential of these cells strongly suggests a beneficial therapeutic combination with existing treatments.
The results presented in the publication show in vivo proof-of-concept for the anti-cancer action resulting from KLRG1 blockade in mouse syngeneic models and highlight KLRG1 as an important driver of adaptive resistance to immunotherapy in humans. Abcuro has discovered KLRG1 blocking antibodies and is developing first-in-class new immunotherapy agents for treatment of cancer.
Abcuro’s mission is to develop a new generation of immunomodulatory therapeutics for treating both autoimmunity and cancer. The company uses proprietary analysis of transcriptome data from human disease to identify new approaches to target key compartments of the immune system. Abcuro was launched in 2016 and is based in Newton, Massachusetts.