Current types of immunotherapies make use of a patient’s own immune cells (T cells) to destroy tumors, including treatment with checkpoint inhibitors. But these treatments do not work in every patient, partly because not all T cells are capable of destroying cancer cells or because the function of the antitumor T cells is suppressed by other signals in the cancer tissue.
In this study, the scientists looked into interleukin-2 (IL2), a powerful secreted protein crucial for activating T cells. Daniela Thommen: “IL2 has been used in the past as a treatment for melanoma and renal carcinoma patients, even before other immunotherapies like checkpoint blockade were developed. However, its use has been limited due to side effects like high toxicity and the activation of regulatory T cells, which suppress the immune system”.
To overcome these limitations, researchers exploited a fresh approach together with Asher Biotherapeutics, a company pioneering new so-called cis-targeting immunotherapies: Fusing IL2 to an anti-CD8 antibody (CD8-IL2) to deliver IL2 specifically to CD8+ T cells, the crucial players of tumor control. This targeted IL2 selectively stimulates antitumor T cells while minimizing activation of immune cells causing immunosuppression or toxicity.
In the lab, the researchers used patient derived tumor tissue to explore the effectiveness of this approach. Their findings were highly promising. Treatment of tumor tissue fragments by CD8-IL2 restored the activity of the dysfunctional T cells making them even more effective than traditional treatments. It also showed efficacy in tumors resistant to checkpoint blockade, suggesting its potential to overcome treatment resistance.
Thommen: “The success of CD8-IL2 opens new avenues for precision immunotherapy, offering a targeted approach to enhance antitumor immunity while minimizing systemic side effects. Further research is needed to optimize the combination of CD8-IL2 with existing therapies like checkpoint blockade, paving the way for more effective treatments for cancer patients.”
NKI researcher Ton Schumacher who was involved in this study, is advisor and scientific advisory board member of and owns stock in Asher Biotherapeutics. The works was funded by Asher Biotherapeutics, by Melanoma Research Alliance Team Science Award, and an institutional grant to the NKI of the Dutch Cancer Society (KWF) and the Dutch Ministry of Health, Welfare and Sport.