In a new study from the University of Virginia, researchers found a way to rescue once-promising immunotherapies for treating solid cancer tumors, such as ovarian, colon and triple-negative breast cancer, that ultimately failed in human clinical trials.
The research explains why antibody approaches effectively killed cancer tumors in lab tests, but proved ineffective in people.
They found that the approaches had an unintended effect on the human immune system that potentially disabled the immune response they sought to enhance.
The new findings allowed the team to increase the approaches’ effectiveness significantly in lab models, reducing tumor size and improving overall survival.
The promising results suggest the renewed potential for the strategies in human patients.
Immunotherapy aims to harness the body’s immune system to recognize and destroy cancer cells.
So far, researchers and protein engineers around the globe, including our research group, were focused on super-charging and super-activating tumor cell-death receptor targeting antibodies in the fight against cancer.
But these therapies have proved less effective against solid tumors than against melanoma (skin cancer) and leukemia (blood cancers).
One major obstacle: It is difficult for immune cells to make their way efficiently into the core of solid tumors.
In the study, the team took a comprehensive approach to harness the power of the immune system to create dual-specificity and clinically effective oncologic therapeutics for solid tumors.
They developed an approach that selectively uses antibodies to target a receptor on the cancer cells’ surface called death receptor-5 (DR5).
This approach essentially tells the cancer cells to die and enhances the permeation of the body’s immune cells into a solid tumor. And it does so without the toxicity associated with chemotherapy.
The findings have strong potential to improve further the clinical efficacy of currently FDA-approved PD-L1 targeting antibodies in solid tumors, particularly the ones approved for deadly triple-negative breast cancer.
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The study is published in EMBO Molecular Medicine. One author of the study is Jogender Tushir-Singh.
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