First-in-Human CISH Inhibitor Trial Yields Positive Data for Metastatic CRC at AACR 2025

 

This breakthrough could redefine immunotherapy, offering new hope for patients with solid tumors who have exhausted conventional treatment options.

Intima Bioscience is working on treatments for solid tumor cancer. They are testing a new way to cure these cancers by developing treatments with small molecules and cell therapy to target the immune checkpoint CISH in patients. This checkpoint has been tough to target with drugs before, but Intima aims to make these therapies accessible to more cancer patients.

Recently, Intima shared results from their first study on humans. They used CRISPR technology to remove the CISH immune checkpoint in T cells, then gave these cells to people with metastatic colorectal cancer. This was presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting.

✔ First Human Trial: Intima Bioscience shared results from the first trial on humans focusing on CISH, a checkpoint inside cells, for people with advanced colorectal cancer that has spread.

✔ CRISPR-Engineered Treatment: The study removed CISH in immune cells found in tumors using CRISPR technology. This checked the new method's safety and success.

✔ Positive Results: A patient with severe colorectal cancer, who did not respond to many treatments, fully recovered for over two years.

✔ Safety Findings: There were no severe side effects or deaths, but some expected blood cell changes occurred.

✔ Potential for Future Therapies: The study suggests more research into blocking the CISH checkpoint. It could lead to new strategies in immunotherapy beyond the common PD-1/PD-L1 treatments.

Industry Impact :- These findings could lead to new drugs targeting CISH and provide more options for treating cancers with solid tumors.

💬 "This clinical trial is the first to test disrupting the CISH gene as a new type of immune checkpoint that could work for many cancers and isn't limited by the tumor's PD-L1 expression. Many studies have highlighted these internal immune checkpoints as promising targets, offering a potential new direction for cancer treatment beyond the current PD1/PD-L1 methods," said Dr. Christopher A. Klebanoff, M.D. a senior advisor and immunotherapy expert at Memorial Sloan Kettering Cancer Center. He is also an Associate Attending, Laboratory Head, and Member of the Immuno-Oncology Program.

Important points about this trial:

👉 The most serious side effects were related to blood issues from chemotherapy or the effects of IL-2, affecting all 12 patients. There were no cases of severe cytokine release syndrome or nerve cell-related immune issues. Targeting the CISH checkpoint did not result in any serious side effects or patient deaths.

👉 A young adult with advanced Stage IV colorectal cancer that didn't respond to previous treatments was treated in this trial. The patient achieved a complete response that has lasted for over two years.

👉 Detailed analysis of this patient showed that T cells with blocked CISH are still active, matching the ongoing complete response to the treatment.

👉 Patients in this trial had a median progression-free survival of 57 days and a median overall survival of 129 days, indicating the advanced stage of cancer in these patients.

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