The battle against cancer is entering a promising new phase with the emergence of targeted treatments designed to attack cancer cells more precisely and with fewer side effects than ever before. While drugs like trastuzumab have become key players in treating cancer by blocking harmful receptors or boosting the body’s immune defense, their success has been limited. This has led to the innovative creation of antibody-drug conjugates (ADCs), a type of therapy that combines antibodies with powerful cancer-fighting drugs. One standout example, a therapy that targets HER2-positive breast cancer, has shown superior results, receiving FDA approval in recent years. Despite these advances, perfecting the balance between effectiveness and safety in these therapies remains a complex challenge.
In a groundbreaking study published in Cell Reports, a team from the National Cancer Institute (NIH) has unveiled a novel therapy that targets CD276/B7-H3, showing significant promise in eliminating cancer. The research, spearheaded by Dr. Brad St. Croix and his colleagues, introduces a new type of ADC named m276-SL-PBD. This therapy is especially effective against tough solid tumors, including those found in triple-negative breast cancer, by combining advanced genetic and chemical engineering techniques to lessen side effects while increasing the therapy’s ability to destroy cancer cells.
The innovation lies in overcoming the challenges of previous ADC therapies, including those targeting CD276, which required high doses and had a narrow window of safety. Through careful drug modification and attachment, and ADC purification, the team has broadened this window, making it possible to eliminate large tumors with much smaller doses. This represents a significant leap in the development of ADCs, offering a powerful and selective approach to targeting solid tumors.
Dr. Brad St. Croix explains, “Our therapy marks a significant advancement in targeted cancer treatment, combining CD276 specificity with a powerful drug to achieve remarkable results in destroying tumors.” He further details their approach, “By finely tuning our ADC therapy using advanced genetic and chemical engineering approaches, we’ve managed to decrease the necessary dosage, thus widening the window of safety and demonstrating superior effectiveness against solid tumors.”
Dr. St. Croix elaborates, “We focused on perfecting the design of our therapy to ensure it delivers the drug effectively to cancer cells while minimizing impact on healthy cells. This careful balance of targeting and drug delivery sets a new standard for the safety and effectiveness of ADCs.” This breakthrough offers new hope for treating a variety of solid tumors, including triple negative breast cancers that do not respond to HER2-targeted treatments and are in urgent need of more effective therapies. As this research moves towards clinical trials, it brings hope for more effective and safer cancer treatments. “What really excites me”, said St. Croix, “is its potential to help cancer patients, especially those with late-stage breast cancer”.
JOURNAL REFERENCE
Yang Feng, Jaewon Lee, Liping Yang, et al., “Engineering CD276/B7-H3-targeted antibody-drug conjugates with enhanced cancer-eradicating capability,” Cell Reports, December 26, 2023. DOI: https://doi.org/10.1016/j.celrep.2023.113503.
