A class of immunotherapies called CD40 agonist antibodies has been under development for 20 years, but has shown limited success in clinical trials. However, a new study published in Cancer Cell presents promising results for a specific antibody, 2141.V11, which was engineered to improve efficacy and reduce side effects.
Researchers at Rockefeller University’s Jeffrey V. Ravetch lab developed 2141.V11, a CD40 agonist antibody that binds tightly to human CD40 receptors and is modified to enhance its crosslinking by engaging a specific Fc receptor. The team then changed the administration route from intravenous to direct injection into tumors, which significantly reduced side effects.
The Phase I clinical trial, which included 12 patients with metastatic cancer, showed promising results. Six patients experienced systemic tumor reduction, with two achieving complete remission in melanoma and breast cancer. Tissue samples revealed immune activity that the drug stimulated, including the formation of tertiary lymphoid structures (TLS), which are associated with improved prognosis and response to immunotherapy.
The study’s findings have sparked interest in further clinical trials for 2141.V11, including Phase I and II studies investigating its effect on specific cancers such as bladder cancer, prostate cancer, and glioblastoma. Researchers hope to identify the indicators of response to this therapy and convert non-responders into responders. With nearly 200 people enrolled in these studies, there is potential for this immunotherapy to become a game-changer in the fight against metastatic cancer.
Source: https://www.genengnews.com/topics/cancer/metastatic-cancers-eliminated-by-cd40-agnostic-antibody