TREATMENT OF LEUKEMIA

Aspects of Cell and Molecular Biology in the Treatment of Leukemia



Aspects of Cell and Molecular Biology in the Treatment of Leukemia

Hypothesis & Aims of this study

Leukemia is a cancer of the blood that causes the cell lines in bone marrow to grow abnormally. This term refers mostly to white blood cells (leukocytes) and is used rarely in reference to red blood cells and platelets. White blood cells are the cells in the blood and tissues that protect animals from infection.

In this Study it is hypothesized that Interferon-alfa-2a (Roche's Roferon-A) is the best treatment of hairy cell leukemia and chronic myelogenous leukemia (CML). The expected result of this study is Cambridge Antibody Technologies is developing the targeted cytotoxin CAT-3888 for multiple forms of B-cell cancer. A disulphide group links a toxin to a murine Ab fragment (i.e., a fragment that contains the combining region of an Ab), which is specific for CD22, a cell surface receptor that is expressed on many B-cell cancers. The cytotoxin moiety of this fusion protein is a modified Pseudomonas exotoxin. Data from a Phase II trial in patients with hairy-cell leukemia was presented at the AACR meeting in April 2006 (Washington, D.C.). In this trial of 25 chemotherapy-resistant patients who received CAT-3888, 44% showed a complete response and an additional 32% showed a partial response to the therapy.

Rationale

The motivation behind this project is that the development of biological products, specifically protein drugs, has been a cornerstone of the biotechnology industry, and it has played a key role in the advancement of cancer treatments over the past 15 years. Biotechnology researchers and companies have used major protein drug technologies - namely, recombinant DNA and monoclonal antibody (MAb) technologies - to design and produce protein drugs directed against cancer. Development of anticancer biological agents has spanned more than three decades, from the overblown excitement over interferons as cancer treatments in the late 1970s and early 1980s (which proved to be largely unfounded) to the marketed drugs of the 1990s and early 21st century. The market for biological anticancer agents exceeded $9.5 billion worldwide in 2005 and has grown at a rate of 20% annually since 2000.

Biological anticancer agents can be subdivided into two categories: agents that directly attack tumors and agents that serve as adjunct therapies designed to ameliorate the side effects of chemotherapy. Although the latter category contains a number of highly successful agents, including the recombinant protein drugs Johnson & Johnson's Procrit (epoetin alfa), Amgen's Aranesp (darbepoetin alfa), Amgen's Neupogen (filgastrim), and Amgen's Neulasta (pegfilgrastim), the majority of new development in this therapeutic area focuses on antitumor agents. Therefore, this report discusses the major classes of antitumor agents, including recombinant cytokines, MAbs, other recombinant proteins, targeted cytotoxins, and radiological agents.

Introduction

A chronic leukemia has a more gradual onset and is caused by the overproduction of mature cells. A chronic leukemia can become an acute leukemia, but the reverse will not happen. An acute leukemia is generally more ominous, especially when it is preceded ...