(by Rachel DeRita, PhD Candidate,Thomas Jefferson University, Department of Cancer Biology). The Abramson Cancer Center at the University of Pennsylvania (UPenn) continues to make innovative advancements in the field of cancer immunotherapy in the midst of what has been called the “immune revolution” by the cancer center’s director, Robert H. Vonderheide (photo), MD, PhD. He explains that the success with the revolutionary immune system-based therapies is “bittersweet,” as many patients are either non-responsive or re-lapse after initial success. A main strategy of the current cancer immunotherapies is to block the immune system’s “off switch.” For example, when the molecule PD-1 on immune cells is bound to PD-L1 on tumor cells, the immune system deactivates and allows the cancer to hide from the immune system. Antibodies against PD-1 (pembrolizumab, brand name Keytruda) can block the deactivation caused by PD-1/PD-L1 binding, and are approved for the first-line treatment of metastatic non-small cell lung cancer with overexpression of PD-L1. Approximately 30% of patients to not respond to this treatment and another 25% exhibit further tumor progression after one year. The search for improvements to current immunotherapies has led to a new class of immunotherapy drugs known as monoclonal antibodies to a protein called CD40. CD40 is expressed by the antigen-presenting cells of the immune system, which are responsible for eliciting an anti-tumor response. When CD40 is bound by other surface markers on T-helper cells, the antigen-presenting cell (such as a B cells or dendritic cells) is activated to perform a number of functions to eventually target and kill tumor cells. By stimulating this molecule with an antibody, the anti-tumor response is strengthened. Dr.
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