Journal of Clinical Investigation Publishes Data Demonstrating Enhanced Antitumor Efficacy of Second Generation
HOUSTON, March 8, 2011 /PRNewswire/ -- Bellicum Pharmaceuticals, Inc. today announced the publication of studies comparing AP1903-activated iMyD88/CD40-transduced dendritic cells (DCs) to conventionally matured DCs, in the April 2011 issue of The Journal of Clinical Investigation (JCI). The studies, conducted by researchers at Baylor College of Medicine, explored the feasibility of a second generation DeCIDe™ vector that combines an inducible toll like receptor (TLR) adapter molecule, iMyD88, with the first generation's inducible CD40 receptor, iCD40.
In the JCI publication, published online on March 7, Narayanan et al reported that chemically induced dimerization (CID) of iMyD88 can replace exogenous, pro-inflammatory adjuvants, providing the danger signal necessary for full DC activation. Moreover, the manuscript shows for the first time that CD40 and MyD88 signaling domains may be fused into the same iMyD88/CD40 chimeric CID protein, which when activated by AP1903 leads to:
- Synergistic activation of downstream signaling molecules in primary DCs.
- Elaboration of high, therapeutic levels of the T helper 1 (Th1) polarizing cytokine, IL-12, leading to the efficient expansion of CD8+ cytotoxic T lymphocytes (CTLs) in vivo.
- Full activation of DCs within lymph nodes, the physiologically appropriate site for activation.
- Elimination of a variety of pre-established tumors in mice, including aggressive B16 melanoma.
"By incorporating TLR signaling into the DeCIDe™ vector, we avoid the need for exogenous TLR adjuvants, while also achieving more potent antitumor activity," stated corresponding author Dr. David Spencer, Vice Chairman of the Department of Pathology and Immunology at Baylor College of Medicine, and Bellicum's Chief Scientific Officer.
Bellicum is working to incorporate this second generation technology into future DeCIDe™ vaccines based on DNA encoding both the iMyD88/CD40 protein and an antigen. In conjunction with a delivery mechanism targeting this DNA to DCs in vivo, such a vaccine could be supplied off the shelf.
About Bellicum Pharmaceuticals
Bellicum Pharmaceuticals, Inc. is developing clinical applications of chemical induction of dimerization (CID), a drug-based remote control technology that extends the physician's reach beyond the point at which a treatment has been administered. Bellicum's mission is to leverage this smart technology to bring safe, effective, innovative cell therapies to market for patients with serious and life threatening diseases. The company's DeCIDe™ vaccines are designed to kill targeted cells by inducing a potent, durable, fully activated antigen-specific T cell immune response. Lead product BPX-101, an autologous DeCIDe™ vaccine, is in clinical development for patients with metastatic castrate resistant prostate cancer (mCRPC). CaspaCIDe™ is a cell therapy safety switch, permitting the rapid elimination of cells in the event of toxicity. CaspaCIDe™ DLI is a donor lymphocyte infusion administered following a hematopoietic stem cell transplant, in which the safety switch may be activated to resolve graft vs. host disease (GvHD). For more information, visit http://www.bellicum.com.
SOURCE Bellicum Pharmaceuticals, Inc.
Posted: March 2011