GUCY2C (Guanylate Cyclase 2C)

P1, N=18, Not yet recruiting, Beijing Immunochina Medical Science & Technology Co., Ltd.

Therapeutic administration of [177Lu]Lu-DOTA-PR15-7 significantly inhibited tumor growth, with standardized tumor volumes at 16 d being markedly smaller than those in the control groups. We have established both optical and radionuclide probes with PR15-7 as a versatile therapeutic strategy, providing valuable insights into targeted therapy for CRC.

Moreover, the BsADC displayed an advantageous safety profile in mice. These findings suggest that the CDH17-GUCY2C BsADC, which induces ferroptosis in tumor cells, could be a promising new treatment for colorectal cancer.

Moreover, the progressive increase in oxidative DNA damage and simultaneous increase in oncogenic events after 28Si exposure also suggest that non-targeted effects might be a significant player in space radiation-induced intestinal cancer development. The correlation between serum 8-OxodG and oncogenic endpoints supports its potential utility as a predictive biomarker of high-LET IR-induced intestinal carcinogenesis, with implications for astronaut health risk monitoring during long-duration space missions.

Furthermore, we validated the direct protein interaction between GPC3 and AFP through immunoprecipitation with purified proteins and through co-localization imaging using immunofluorescence microscopy. This study provides large proteomic datasets related to GPC3-associated proteins, enhancing our understanding of glypican biology in cancer cells and offering a new approach to identifying immunotherapy targets.

This study demonstrated a potent GUCY2C-targeted CAR-T cell for gastrointestinal tumor therapy and highlights the importance of adequate tonic signaling for effective CAR-T cell therapy against solid tumors.

This results in increased production of inflammatory cytokines and granzyme B, improved cytolytic effector function with low antigen-expressing tumor cells, and robust anti-tumor efficacy in vivo compared with the CD28 structural domain CAR. This suggests that CD8α structural domains should be considered in the design of all CARs for the generation of high-affinity CARs and optimally effective CAR-T cells in solid tumor immunotherapy.

P1, N=30, Recruiting, Second Affiliated Hospital of Guangzhou Medical University | Trial completion date: Aug 2026 --> Aug 2036 | Trial primary completion date: Aug 2024 --> Aug 2026

These miRNAs may contribute to GUCY2C dysregulation by downregulating GUCA2B, which encodes uroguanylin. Consequently, hsa-miR-182-5p and hsa-miR-27a-3p show promise as potential targets for early intervention and treatment in the early stages of CRC.

GUC is expressed across GI cancers and GUC-H tumors are characterized by an "immune cold" TIME but longer OS. These results should be taken into consideration while evaluating the clinical utility of GUC as a novel immunotherapy target in advanced GI cancers that historically have not responded to ICI.

Study enrollment is ongoing. Clinical trial information: NCT04111172.