Sorrento Therapeutics, an oncology company based in San Diego, Calif., and Conkwest, a Cardiff-by-the-Sea, Calif.-based, privately-held immuno-oncology company developing proprietary Neukoplast (NK-92), a natural killer cell-line based therapy, have entered into a definitive agreement to jointly develop next generation CAR-TNK immunotherapies for the treatment of cancer.
The CAR-TNK technology platform combines Conkwest's proprietary Neukoplast cell line with Sorrento's proprietary G-MAB fully human antibody technology and CAR designs to further enhance the potency and targeting of Neukoplast. Sorrento and Conkwest will establish an exclusive global strategic collaboration focused on accelerating the development of CAR-TNKs for the treatment of hematological malignancies as well as solid tumors.
Both companies will jointly own and share development costs and revenues from any developed CAR-TNK products. Sorrento will make a $9 million strategic equity investment in Conkwest and provide $2 million in research credit payments towards the development of novel CAR-TNK cell lines.
Adoptive immunotherapy is widely regarded as one of the most impactful and innovative anti-cancer therapy breakthroughs. To date, T-cell based therapies, like CAR-T, have shown the most promise in select hematologic cancers, especially B-cell malignancies such as acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL). They also have demonstrated outstanding therapeutic impact, including a high percentage of complete responses (CRs) in leukemia patients using CD19-CAR-T cells.
While the clinical results seen have been promising, CAR-T therapies have been associated with some concerning side effects, especially potentially fatal cytokine-release syndrome that is mediated by interleukin-6 (IL-6) released from the T-cells and characterized by high fevers and sudden drops in blood pressure. Afflicted patients often require aggressive support in an intensive care unit setting. Most current CAR-T approaches rely upon patient derived T-cells, which require individualized processing, and are thus challenging with regard to commercial scalability, quality control and consistency. Furthermore, this process relies on the ability to obtain sufficient numbers of the patients' own immune T-cells to make adequate doses of CAR-T cells.
The "off-the-shelf" CAR-TNK approach will utilize Conkwest's bioreactor-grown NK-92 cell line, Neukoplast, as the immune effector cells. Among the many features that distinguish Neukoplast from patient derived T-cells are the lack of IL-6 expression (the most common mediator of cytokine release syndrome), an innate capability of destroying a broad range of cancer cells as well as cancer stem cells and scalability with batch-to-batch consistency. These Neukoplast cells can be re-engineered in a virus-free process to express surface receptors using Sorrento's G-MAB library to yield a stable line of effector cells that recognize and target specific antigens on tumor cells. The CAR-TNK cells also can be generated and produced in large quantities, thereby obviating the need for expensive, decentralized biologistics—a critical drawback of current CAR-T and dendritic cell therapies.