Multimeric Biotherapeutics, Inc.

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CD40-B Cells for Immunotherapy

In 1991, Banchereau et al. described a method for growing B cells from human blood using a CD40 stimulus plus IL-4. In 1997, Schultze et al. showed that these "CD40-B cells" were antigen-presenting cells (APCs) that could be used to generate anti-tumor CD8+ cytotoxic T lymphocytes (CTLs) for cancer therapy. Using B cell lines generated by the Epstein-Barr virus (EBV), Heslop et al. showed that CTLs could be generated in vitro that, upon infusion into patients, reliably cured them of EBV-related lymphomas. While this approach could potentially be extended to all types of cancer, the process of making CD40-B cells has been impeded by the lack of a soluble, cell-free form of CD40L. Multimeric has now found that UltraCD40L™ (SP-D-CD40L) combined with IL-4 rapidly generates CD40-B cells from just a single tube of blood within 2 weeks.

CD40-B cells

The picture was taken looking up at the bottom of a vertical culture flask in which about 200 million CD40-B cells were grown from a single tube of blood in only 12 days using UltraCD40L™ and IL-4. This marks the first time that human B cells can be conveniently grown from patients without using complicated culture conditions that involve a second cell type to supply the required CD40L stimulus.