Tumor-specific extracellular ribonucleoprotein complex (eRNP complex)

The tumor-specific extracellular ribonucleoprotein (RNP) complex is a novel therapeutic target identified through target-agnostic profiling of the human immune response in cancer patients. This complex prominently features a differentiated form of Poly(A)-binding protein 1 (PABP-1) bound to RNA and is selectively expressed on the surface of various solid tumor cells, including non-small cell lung cancer, breast, and colorectal cancers, while remaining absent from normal tissues (Scholz et al., 2022). The presentation of this complex on the cell surface is believed to be induced by cellular stress, including stress from chemotherapy, making it a marker of the tumor microenvironment's immunogenicity (Atreca, 2020). It is targeted by the engineered antibody ATRC-101, which binds to the complex and initiates a multi-step immune response termed 'Driver Antigen Engagement.' This mechanism involves the activation of innate myeloid cells, particularly dendritic cells, which then drive an adaptive immune response characterized by the recruitment and activation of CD8+ T cells and natural killer (NK) cells to destroy the tumor (PNAS, 2022). Although development of the lead candidate ATRC-101 was paused, the target remains a significant example of using patient-derived antibodies to discover novel extracellular markers for immunotherapy.

Other names

Extracellular ribonucleoprotein complexATRC-101 targetPABP-1-containing RNP complexTumor-associated RNP complexTumor-specific extracellular ribonucleoprotein complex on cancer cells

ATRC-101 binds to the extracellular RNP complex on tumor cells, which is induced by cellular stress. This binding activates the innate immune system, specifically myeloid cells such as conventional dendritic cells (cDC1), which subsequently drive a potent adaptive immune response involving the recruitment and activation of CD8+ T cells and natural killer (NK) cells to eliminate the tumor.