On May 14, 2024 Alchemab Therapeutics (Alchemab), an antibody discovery company identifying naturally occurring antibodies from individuals resilient to disease, reported the publication of a peer reviewed article titled "Predictability of B cell clonal persistence and immunosurveillance in breast cancer" in the journal Nature Immunology (Press release, Alchemab Therapeutics, MAY 14, 2024, View Source [SID1234643270]). The senior author Rachael Bashford-Rogers is a co-founder of Alchemab and the paper was a collaboration between the Cancer Dynamics Group at The Institute of Cancer Research, London, (ICR), the University of Oxford, the University of Cambridge and Alchemab.
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Alchemab is building a broad pipeline of protective therapeutics for hard-to-treat diseases, with an initial focus on neurodegenerative conditions and oncology. The Company has developed a highly differentiated platform which enables the identification of novel drug targets and therapeutics by analysis of patient antibody repertoires. The platform uses well-defined patient samples, deep B cell sequencing, and computational analysis to identify convergent protective antibody responses among individuals that are susceptible but resilient to specific diseases.
In cancer, Alchemab focuses on identifying antibodies from patients with certain solid tumors who are long-term survivors of the disease. In preliminary work, Alchemab has identified antibodies associated with checkpoint inhibition, angiogenesis, and cytokine modulation in cancer survivors. The opportunity to identify novel antibodies and targets associated with cancer survivors represents a unique approach to therapeutic development in oncology.
Jane Osbourn OBE, Chief Scientific Officer and Co-Founder of Alchemab, said: "Immunotherapies have transformed the outlook for a range of different cancers but, unfortunately, they still only work for a minority of patients. We are making great strides in our understanding of the role of B cells in the adaptive immune system, but if we are to develop broader and better immunotherapies, overcoming limitations of existing treatments, we need a deeper understanding of how they interact with cancer as it grows and spreads. This paper has given us an important perspective on the role that B cells play in the immune response to cancer and that will help us to develop improved therapies to treat these deadly diseases."
A comprehensive analysis of breast cancer immunosurveillance in biopsy tissue from metastatic and early breast cancer patients was performed in the study. By integrating B Cell Receptor (BCR), T Cell Receptor (TCR), DNA and RNA-sequencing (RNA-seq) data from patients with multiple metastatic tumor sites, and during neoadjuvant (chemo) therapy in early disease patients, clones were tracked and characterized that were persistent over time throughout therapy and across metastatic sites. Results showed that both B cell and T cell responses in each patient seem to coevolve with the metastatic cancer genomes and mirror the tumor mutational and neoantigen architecture. B cell clones associated with metastatic immunosurveillance and temporal persistence were more expanded and distinct from B cell clones found in single metastatic sites. B cell clonal immunosurveillance and temporal persistence are predictable based on the deep sequence analysis, which enables assessment of clonal relatedness. This predictability was generalizable across other immune-mediated disorders.
This work helps lay a foundation for Alchemab to prioritize antibody sequences for therapeutic targeting in cancer and immune disorders.