CAR T-cell therapy enters into Phase I clinical trial

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Cancer fighting chimeric antigen receptor (CAR) T cells, developed in the Sentman laboratory of Dartmouth's Norris Cotton Cancer Center, are taking the next step into a Phase I clinical trial beginning early in 2015. Charles Sentman, PhD, first published this novel work with CAR T cells in Blood in 2005 and in Cancer Research in 2006. They demonstrated that their CAR therapies may have broad applicability for many different cancers, and further found that CAR therapy not only eliminated tumors from animals, but also prevented cancer recurrence. Professor Sentman is one of the Scientific Founders of Celdara Medical, LLC (CM), and has been collaborating with CM to translate this work to the clinic. On January 6, Cardio3 BioSciences announced the acquisition of OnCyte, LLC, a division of CM comprising these technologies, to further advance the therapies.

The first therapy to move to a clinical trial is CM-CS1, an autologous CAR T-cell therapy that employs NKG2D, which is a "natural killer" cell receptor designed to target ligands present on most tumor types, including both hematologic cancers and solid tumors. Many cancers are known to express these targets, including cancers of the pancreas, breast, and prostate. The current clinical trial is in hematologic cancers (i.e. cancers of the blood) such as leukemia and myeloma. The possibility of broad application holds great promise.

Several other related therapies, as well as a next generation platform technology, are in preclinical development. The next generation platform from Sentman's lab combines CAR T cells with another innovation they developed called TCR-inhibiting molecules (TIMs). TIMs are designed to allow CAR therapy to be used with T cells from healthy donors yet avoid Graft-versus-Host-Disease (GVHD). If successful, the TIM/CAR approach will reduce time to treatment, simplify logistics, and significantly decrease costs.

"We are very excited about the opportunity to move these novel therapies into the clinic," Sentman said." It is an exciting time in cancer immunotherapy, and the potential of CAR cell therapies holds great promise to improve patients' health."

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