Immune checkpoint inhibitors have made significant progress in cancer treatment, but not all patients respond to these therapies, and some develop resistance over time. To overcome this challenge, researchers are focusing on other immune pathways in the body, like the Toll-like receptor signaling, which can help the immune system attack tumors. However, treatments that stimulate these pathways across the whole body can lead to harmful side effects. This is why there is a need for more targeted therapies.

One promising approach is using immune-stimulating antibody conjugates (ISACs), which are designed to deliver immune-boosting agents directly to cancer cells or immune cells in the tumor. While ISACs have shown potential, many clinical trials have been halted because they did not work well enough or caused side effects. Therefore, it is important to improve the design of these therapies to make them more effective and less harmful.

Our team has developed new technology for creating antibody-drug conjugates (ADCs), which include stable linkers and chemical linking methods that help make these therapies more uniform. Using this technology, we have created a conjugate that activates the immune system and successfully slowed tumor growth in a mouse model by priming a specific type of immune cell (CD8+ T cells) to attack the tumor.

Building on these results, we believe our new platform, Neo-ISAC, which targets tumor-specific mutations, will enhance the immune system’s response to cancer while reducing harmful side effects. Our research will focus on two main goals: First, we aim to establish a reliable method to create Neo-ISACs. Second, we will evaluate how well these therapies work against tumors and their safety in preclinical models, including testing the immune response and studying potential toxicity. This research will provide key insights into how to improve the Neo-ISAC platform and move toward future clinical applications.