This project, led by Jacques Galipaeu, MD, aimed to to generate the data needed to secure Investigative New Drug licenses from the Food and Drug Administration (FDA) to use personalized GIFT4 B cells to treat cancer as part of first-in-human clinical trials at the UW Carbone Cancer Center. Previous work enabled researchers to convert normal mouse B cells to cancer-killing cells by treating them with a synthetic cell-signaling protein called GIFT4, and the resulting cells were able to initiate an anti-tumor immune response even in the absence of defined tumor markers. In this work, researchers tested these GIFT4 B cells in mice with prostate and neuroblastoma tumors to see if the cells could improve the immune system’s ability to fight cancer.
The researchers made significant progress toward their goal. They found that B cells, when grown with dendritic cells and exposed to GIFT4 protein, could activate T cells which then target tumors. These findings demonstrated the importance of understanding B cell-dendritic cell interactions to advance cancer vaccine development. Additionally, combining GIFT4 B cells with radiation and immunotherapies improved survival, highlighting the efficacy of multifaceted therapies in targeting cancer. Overall, these results have the potential to enhance cell therapies leading to more effective treatment strategies for cancer in the future.
The Challenge
Cancer immunotherapy is an established and rapidly growing field that is poised to offer novel and powerful ways to treat cancer. However, there are obstacles that are yet to be addressed including off-target adverse events, efficacy and dose refinement. Recent research advances suggest that harnessing the human immune system could be the most effective approach to overcome the current challenges in the field of cancer immunotherapy.
Researchers at the University of Wisconsin–Madison have proposed a new way to treat prostate cancer and pediatric neuroblastoma using a patient’s own B cells. In mouse models, researchers were able to convert normal mouse B cells to cancer-killing cells by treating them with a synthetic cell-signaling protein, called GIFT4. The GIFT4 B cells are able to initiate an anti-tumor immune response even in the absence of defined tumor markers.
Project Goals
The overarching goal of this project was to generate the data needed to secure Investigative New Drug licenses from the Food and Drug Administration (FDA) to use personalized GIFT4 B cells to treat cancer as part of first-in-human clinical trials at the UW Carbone Cancer Center. This data was gathered by testing GIFT4 B cells in mice with prostate and neuroblastoma tumors to see if it could improve the mice immune system’s ability to fight cancer.
Results
Researchers made significant progress toward their goals. First, in mice with prostate tumors, researchers discovered that when B cells were grown together with dendritic cells and exposed to GIFT4 protein, they could successfully trigger the activation of T cells, which are immune cells that target tumors. Notably, only B cells demonstrated the ability to activate T cells. Additionally, the researchers established that B cells require direct interaction with dendritic cells for this process to occur effectively. They proposed that gaining a deeper understanding of the interactions between B cells and dendritic cells is crucial for enhancing the development of cancer vaccines and future research is needed in this area.
Second, the research team assessed whether the inclusion of GIFT4 B cells in a combined therapeutic approach would enhance the therapy’s efficacy in targeting neuroblastoma tumors in mice. They observed that the addition of GIFT4 B cells resulted in a slight improvement in survival rates when administered along with the combination treatment. They also discovered that the GIFT4 B cells were present in the lymph nodes near the tumor only when combined with the full treatment, not when used alone. This suggested that the combined treatment helped the GIFT4 B cells better target the tumor. These findings demonstrated that using multiple treatments together, like radiation and immunotherapy, is important for making cell therapy more effective against cancer.
Lasting Impact
The knowledge and partnerships gained from this project have led to the launch of a new Cancer Immunotherapy Program at UW Health’s Carbone Cancer Center where Drs. Galipeau, Sondel and McNeel serve as senior leadership to a growing team of faculty engaged in developing cancer cell therapy. Novel partnerships arising from and related to this work will advance access to investigational cancer therapeutics for Wisconsinites with unmet medical needs in oncology.
