Abstract A090: Novel immunotherapy targeting tumor-induced immune disorder reverses cancer cachexia and prolongs survival

Abstract Introduction: Cancer cachexia is generally recognized as a complex syndrome due to the multiple symptoms that patients suffer including body weight loss, muscle wasting, anorexia, fatigue etc. Despite intense efforts to investigate the mechanisms of those symptoms, the cause of cancer cachexia is still not fully understood. The lack of understanding of the causative mechanisms of cancer cachexia has hindered the development of successful treatments. Given cachexia’s profound effect on multiple organs, it’s clear that the driving mechanism impacts the whole body. Also, since cancer cachexia and immune system disorder coexist in late-stage cancer patients, we look to investigate the role of the immune disorder in cancer cachexia and explore novel immunomodulatory interventions. Methods: To establish cancer cachexia model, 7-week-old BALB/c mice were inoculated with 1 x106 C26 tumor cells subcutaneously. Immunomodulator, R-Ketorolac was given through oral gavage. Results: Significant and multifaceted abnormalities of the immune system underlines cancer cachexia onset and development, including abnormal expression of destructive inflammatory cytokines and dysregulation of multiple immune cell populations. Abnormal expression appears earlier than mice showing cachectic symptoms. Cachexia symptoms begin to manifest when immune abnormalities exceed a certain threshold. Using a newly identified immunomodulator, R-Ketorolac, we found that severe cancer cachexia could be fully reversed. Survival was maintained until termination due to protocol limitation on tumor size. Further studies revealed that R-Ketorolac modulated both cytokine expression and immune cell populations toward a balanced state, thus representing a new type of immunotherapy. This interesting finding from animal studies has been clinically validated on advanced pancreatic cancer patients with cachexia. Conclusion: Cancer cachexia could be completely reversed by a novel immunomodulator, which not only opens a new direction to understanding the mechanism of cancer cachexia and developing long-awaited effective treatments for this lethal syndrome, but also provides a new avenue to create life-saving cancer immunotherapies. Citation Format: Lingbing Zhang. Novel immunotherapy targeting tumor-induced immune disorder reverses cancer cachexia and prolongs survival [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A090.