The search of new drugs is ongoing and challenging for all diseases, including cancer which is becoming the worldwide number one killer of patients. As a sub-category of cancer, leukemia diagnoses are wide-spread and leukemia often may develop a resistance to existing drugs. With this in mind, developing and discovery of new medication for leukemia and other cancers is an objective of many researchers around the world.
Leukemia is a malignant progressive disease in which the bone marrow and other blood-forming organs produce increased numbers of immature or abnormal leukocytes. These abnormal leukocytes suppress the production of normal blood cells, leading to anemia and other symptoms. Leukemia presents in patients in several forms including acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML), as well as a number of less common types. Leukemia and lymphoma both belong to a broader group of tumors that affect the blood, bone marrow, and lymphoid system, known as tumors of the hematopoietic and lymphoid tissues.
Treatment may involve a combination of chemotherapy, radiation therapy, targeted therapy, and bone marrow transplant, in addition to supportive care and palliative care as needed. The success of treatment depends on the type of leukemia and the age of the person. Outcomes have improved in the developed world. The average five-year survival rate is 57% in the United States. In children under 15, the five-year survival rate is greater than 60% to 85%, depending on the type of leukemia. In children with acute leukemia who are cancer-free after five years, the cancer is unlikely to return. Roughly 90% of all leukemias are diagnosed in adults, with AML and CLL being most common in adults.
A form of targeted therapy in use is antibody-drug conjugates (ADCs). ADCs combine the specificity and targeting of high affinity antibodies with the cytotoxicity of a therapeutic agent, such as cytotoxic agents, biological response modifiers, enzymes, apoptosis-inducing agents, and radioisotopes. Release of therapeutic agents from the antibody can require trafficking and localization of the antibody-drug conjugate to lysosomes.
In view of the forgoing, this invention is developed to provide an ADC for the targeted therapy of leukemia as one of its objectives . It is a further objective to repurpose off-patent drugs for leukemia.