In March 2015 HaemaLogiX acquired the assets of Immune System Therapeutics (IST) including its lead drug MDX-1097 or IST-1097 (now called KappaMab). KappaMab is an antibody (a large protein) that is in a new class of medicines being developed to treat a fatal form of cancer known as multiple myeloma or plasma cell myeloma. In myeloma, malignant plasma cells, which are a type of B cell, accumulate in the bone marrow and are responsible for progression of the disease. KappaMab targets these malignant plasma cells as described below.
These malignant plasma cells produce a protein on their cell surface that has been identified as the Kappa Myeloma Antigen (KMA). KMA is not found on normal (healthy) plasma cells or B-cells, nor on any other normal human tissue and it is believed to be a marker specific to those abnormal cells. The antibody, KappaMab, was created to specifically bind to this KMA in the bone marrow of myeloma patients. When the antibody attaches to KMA, effector cells from the patient's own immune system recognize that the myeloma cell is tagged and should be destroyed. This is a normal defense mechanism of the immune system and is called antibody dependent cellular cytotoxicity (ADCC). Basically, the antibody induces or activates the immune system to attack and destroy these antibody-tagged cells.
Myeloma is a clonal disease, in other words all the malignant plasma cells in the bone marrow have developed from a single parent cell. There are two types of clones; the parent cell can be kappa-type, which have KMA on their cell surface as described above, or lambda-type which have LMA (lambda myeloma antigen) on their cell surface. In general two thirds (~70%) of myeloma patients cells express KMA and one third (~30%) express LMA.
HaemaLogiX has acquired LambdaMab antibodies, which specifically target the form of myeloma that expresses LMA. These antibodies are in preclinical development for the treatment of myeloma and a rare form of myeloma called POEMS-1 syndrome, where almost all patients have lambda-type disease.
The HaemaLogiX antibodies, KappaMab and LambdaMab have been shown to specifically target KMA and LMA on malignant plasma cells. Using these antibodies, two types of Chimeric Antigen Receptor-T cells (CAR-T cells) are being created; KMA.CAR-T cells and LMA.CAR-T cells. The KMA.CAR-T cells are currently in preclinical development and will soon be tested in nonclinical studies before a clinical trial is initiated to treat patients with kappa-type myeloma. A similar approach will be taken for the development of the LMA.CAR-T cells for patients with lambda-type myeloma. The general process for creating CAR-T cells is shown in the figure below.