CNDO-109 - Activates NK cells

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CNDO-109

OVERVIEW

PIPELINE

CNDO-201

CNDO-109

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Another common therapy, established almost 15 years ago at the National Cancer Institute by Dr. Rosenberg and his colleagues, activates the innate immune system with the administration of high dose Interleukin-2 ("IL-2"). Through binding to the IL-2 receptor, IL-2 activates NK cells to attack cancer cells. After high-dose IL-2 therapy, NK cells are activated to search out and kill cancer cells. Unfortunately, the use of IL-2 therapy is limited because of its side effects, which include severe life-threatening infusion reactions and induction of autoimmune disease.

The importance of NK cells in the host system’s defense against cancer was recognized by Professor Mark Lowdell at the Royal Free Hospital in London and others when they noted that patients who could mount an immune response to their AML became long-term survivors after chemotherapy. See Figure 1. Researchers identified that a key to the successful immune response of host systems was the NK cell. Expanding on pioneering work by the Perugia group in the treatment of high-risk leukemia patients with highly engineered haploidentical bone marrow transplantation, Lowdell et al determined that activated NK cells were the key to eliminating AML cells and that NK cells require two signals to kill a tumor cell – a priming signal followed by a trigger signal. NK-sensitive tumor cells provide both signals and the cancer is eliminated. NK-resistant tumors are not destroyed since they only provide one signal "trigger". NK cells which have not been primed cannot respond to the trigger. The "priming signal" can be provided by either cytokines, such as high dose IL-2 or IL-15 or by CNDO-109. In contrast to IL-2 or IL-15, NK cells activated by CNDO-109 (known as Tumor Activated NK cells) retain their activated state after cryopreservation and thawing. This allows commercialization of the process since the NK cells can be activated with CNDO-109 and prepared at a manufacturing facility under GMP conditions and shipped to the clinical center as a frozen patient-specific dose, ready for infusion.

Although AML is the prototype tumor lysed by CNDO-109 activated NK cells, CNDO-109 activated NK cells are expected to be active against most cancer types. Based on preclinical efficacy studies of CNDO-109 conducted by Professor Lowdell at the Royal Free Hospital in London using human specimens of prostrate, breast and ovarian cancer. Coronado expects CNDO-109 to be active against tumors that have been successfully treated by high dose IL-2 therapy such as renal cell carcinoma and melanoma.

Figure 1: Long-term survivors of AML () developed leukemic cytotoxic activity (“LCA”) > 12.5% to their presentation disease. Patients with LCA < 12.5% () had a worse outcome. The cells responsible for LCA are NK cells. "CR" means complete response.

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