#United States #New York #Colorectal Cancer #CISH immune checkpoint #Intima Bioscience

Landmark Presentation on CISH Immune Checkpoint at AACR 2025

In an exciting advancement in oncology, Intima Bioscience, a clinical stage company specializing in solid tumor cancers, showcased groundbreaking data from a groundbreaking first-in-human clinical trial at the 2025 American Association for Cancer Research (AACR) Annual Meeting. The study focused on the intracellular immune checkpoint known as CISH, unveiling promising results in patients battling metastatic colorectal cancer.

A New Era in Immunotherapy

One of the principal investigators, Dr. Emil Lou, a professor of Hematology and Oncology at the University of Minnesota, emphasized the significance of this study in the realm of immunotherapy. For the past decade, researchers have predominantly centered their efforts on neutralizing cell surface targets. However, the potential of intracellular checkpoint targets, such as CISH, has been largely overlooked despite their dramatic anti-cancer potential. The findings from this trial aim to pave the way for novel therapeutic strategies in solid tumor immunotherapy.

Study Methodology

The research involved the innovative application of CRISPR technology to knock out the CISH gene in tumor-infiltrating lymphocytes (TILs). The team administered these genetically modified T cells to patients diagnosed with metastatic colorectal cancer who had exhausted multiple treatment options, including conventional chemotherapy and immunotherapy. The results were revealing:

• - Notably, a patient diagnosed with young adult colorectal cancer achieved a complete clinical response, which has continued for two years post-treatment.
• - Molecular and genetic evaluations confirmed the ongoing presence of CISH-inhibited T cells, correlating with this long-lasting therapeutic response.

Dr. Lou noted, "This clinical trial represents a paradigm shift in cancer treatment. By genetically disrupting CISH, we could potentially unlock new avenues for broader immunotherapeutic applications that are not hindered by the tumor's surface PD-L1 expression."

Patient Safety and Trial Outcomes

The safety profile of the treatment demonstrated that most severe adverse events were attributable to the preparatory regimen rather than the therapeutic agent targeting CISH. Remarkably, there were no instances of severe cytokine release syndromes or neurotoxicity associated with the immune effector cells in any of the participants.
Despite the advanced stage of cancer in the patient population, characterized by a median progression-free survival of 57 days and an overall survival of 129 days, the achieved complete response in one patient marks a significant milestone in seeking viable treatments.

Implications for Future Therapies

Alongside the presentation at the AACR, an accompanying scientific paper titled "CISH: A Novel Intracellular Immune Checkpoint" has been submitted for peer review, further exploring the therapeutic potential of CISH in both standalone and combination immunotherapy settings. According to Dr. Christopher A. Klebanoff from the Memorial Sloan Kettering Cancer Center, this study strongly supports CISH as a target that could revolutionize how patients respond to immunotherapy across various cancer types.

Conclusion

The findings presented by Intima Bioscience at AACR 2025 represent not just a leap in understanding CISH’s role but also herald the development of next-generation small molecule therapeutics targeting this immune checkpoint. This could democratize access to effective treatments for patients worldwide, particularly those experiencing the dire challenges faced in the late stages of colorectal cancer.

Overall, the results from this innovative clinical trial offer new hope and pave the way for future research aimed at conquering tumors previously deemed undruggable. As Dr. Lou summarizes, "In metastatic colorectal cancer, where treatment options remain scant, CISH presents an exciting opportunity to change the status quo of current therapies and improve clinical outcomes for patients."