Vaccinex (VCNX) will present new data characterizing the unique mechanism of pepinemab to enhance immune responses to checkpoint therapies in the neoadjuvant setting that are associated with improved pathologic response in patients with head and neck cancer. Lead investigator and collaborator, Conor Steuer, MD from Winship Cancer Center at Emory University, will present results at the 2025 Annual Meeting of Clinical Oncology in Chicago on June 1, 2025. Previously reported data from our collaboration with Emory University suggest a crucial role of pepinemab treatment in melanoma patients to facilitate immune cell interactions within highly organized and robust centers of immunity, called tertiary lymphoid structures, or TLS. By blocking the SEMA4D inhibitory signal to Dendritic Cells, pepinemab allows productive, coordinated interactions between SEMA4D+ T cells, key effector cells capable of eradicating tumors, and DC, regulatory cells that promote immune cell interactions within TLS so as to amplify mature T cell responses. New data presented at ASCO will characterize the mechanisms of neoadjuvant treatment with pepinemab in patients with resectable head and neck cancer. Standard of care for these patients often involves toxic chemotherapy and/or radiotherapy, in addition to surgery, which can significantly impact their quality of life. Peri-operative treatment with immunotherapy has recently reported promising and potentially practice-changing results. Certain HNSCC with hot beds of immune cells organized into TLS have been shown to correlate with clinical benefit and positive response to immune checkpoint therapy. However, many HNSCC are considered immunologically “cold” tumors, due to exclusion of immune cells from tumor and/or high levels of immune suppressor cells, making them resistant to immune checkpoint therapy. Pepinemab has potential to be a major advance for HNSCC patients with cold and resistant disease, with capacity of a well-tolerated and effective treatment that can induce formation and harness the power of TLS to optimize the clinical benefit of immunotherapy. Our data demonstrate that the addition of pepinemab to neoadjuvant immune checkpoint treatments did not compound toxicities, yet it enhanced TLS maturity that correlated with improved pathologic response. Collectively, these results highlight the potential of pepinemab to turn immunologically cold tumors, such as HPV-negative head and neck cancer, into hot immune centers by inducing robust and mature TLS.
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