On June 26, 2023 Larkspur Biosciences reported it revealed that one of their lead programs is a first-in-class B cell checkpoint, TIM-1 (Press release, Larkspur Biosciences, JUN 26, 2023, View Source [SID1234633156]). This announcement follows the publication by Larkspur co-founder Vijay K. Kuchroo, DVM, PhD (Samuel L. Wasserstrom Professor, Neurology, Harvard Medical School; Senior Scientist, Neurology, Brigham and Women’s Hospital) in the journal Nature of TIM-1 as a targetable checkpoint protein central to B-cell anti-tumor activity.
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Immunotherapies targeting T cells have transformed the treatment of many types of cancers. Recent discoveries have highlighted that the presence of tertiary lymphoid structures in tumors – areas of B cell and T cell activation – are associated with positive responses to checkpoint blockade. Larkspur’s approach addresses the unique ways that tumors hijack the immune system, targeting bottlenecks that tumors use to subvert the immune system in order to develop precision immunotherapies for molecularly defined patient populations. This newly disclosed program adds a unique way to use B cells to drive anti-tumor responses.
"The discovery of this novel B cell checkpoint protein, outlined in the Nature publication, unlocks the potential of targeting B cells to enhance immunotherapy responses," said Dr. Kuchroo. "These findings support broadening the application of immune checkpoint blockade in cancer immunotherapy and provide a clear path to translation, which Larkspur is advancing within its pipeline."
Dr. Kuchroo, along with lead author Lloyd Bod, PhD (Mass General Cancer Center), and colleagues, discovered a type of B cell expressing TIM-1 expanded as tumors grew in melanoma. Using an antibody to TIM-1, they discovered that targeting TIM-1 and PD-1 in the melanoma model led to a better anti-tumor response, underscoring the potential of targeting both B cells and T cells in cancer.
"It has recently been shown that the presence of B cells at the tumor is associated with positive responses to checkpoint blockade for cancer patients," said Catherine Sabatos-Peyton, PhD, CEO of Larkspur Biosciences. "TIM-1 offers a novel way to harness the power of B cells at the tumor and potentially drive more meaningful anti-tumor responses for more patients. We look forward to continuing to progress our TIM-1 program as part of our mission to create the next precision immunotherapies to outsmart cancer."
The Nature article titled "B-cell-specific checkpoint molecules that regulate anti-tumour immunity" was published on June 21, 2023. The research briefing "Uncovering a role for B cells in antitumour immunity" provides a summary of the article.