ISF35 Technology

Memgen believes that truly effective and non-toxic therapies against cancer can be achieved by activating the human immune system to generate a host anti-tumor immune response. Towards this end, Memgen is focused on the development of a new series of molecules that improve the therapeutic potential of the various tumor necrosis factor (TNF) molecules, a large family of proteins with diverse roles in immune regulation.

ISF35

Memgen's first TNF family derived product, ISF35 (Figure 1), is a recombinant protein molecule that binds and activates human CD40+ B lymphocytes that are found on a vast majority of malignant leukemias and lymphomas. In a Phase I clinical trial, ISF35 delivered with a human adenovirus type 5 (Ad-ISF35) exhibited significant activity (as measured by drops in absolute lymphocyte counts and decreases in lymph node sizes) against malignant leukemic cells found in patients with chronic lymphocytic leukemia (CLL).

Figure 1. The linear structure of ISF35, a chimeric molecule. The molecule has been engineered to maximize the CD40 binding activity while decreasing, if not eliminating, the toxicities of the parent human and murine CD154 molecules. The white regions represent areas that have human amino acid content. The blue bars represent regions that retain amino acids found in the murine CD154 molecule. The green bar represents a region removed from the human molecule that stabilizes the molecule on the surface of human CD40+ cells.

The benefits of ISF35 technology may not be limited to CLL treatment. Because it is a potent immunostimulatory molecule, ISF35 could provide the foundation for therapies directed toward solid tumor cancers such as malignant melanoma, breast, colon, ovarian and lung cancers. Preclinical studies have already been completed that demonstrate a potential role for ISF35 in the treatment of these malignancies.

Memgen's recombinant ISF35 molecule is a novel CD40 binding protein engineered to be an immune-stimulant that maximizes the clinical activity of the molecule while eliminating the toxicities associated with its parent molecule CD154 (CD40-ligand). ISF35's high therapeutic index (activity versus toxicity) is due to the delivery of this potent molecule in a membrane-bound form that is not cleaved into toxic metabolites. As a single agent in pre-clinical studies, ISF35 has demonstrated compelling activity against B cell leukemias and lymphomas resulting in acute and long lasting responses against these diseases. The in vivo activation of malignant B lymphocytes and the up-regulation of pro-apoptotic factors by ISF35 will enhance the sensitivities of these cancers to standard therapies including patients who have developed resistance to standard treatment protocols.

Clinical Trials

ISF35 is currently in clinical trials. Please see the Clinical Trials page for more details.