Esophageal Cancer involves the organ called the esophagus. Esophagus is a muscular tube that joins the mouth and the stomach. The most common region where cancer develops in the esophagus is the lining. Degeneration of squamous cells, which constitutes most of the lining, leads into a malignant tumor and is called squamous cell cancer. Towards the bottom, where it joins the stomach, the esophagus is lined with columnar cells. Esophageal Cancer (malignant) of such columnar cells is known as adenocarcinoma.

Esophageal carcinoma arises in the mucosa. Subsequently, it tends to invade the submucosa and the muscular layer and, eventually, contiguous structures such as the tracheobronchial tree, the aorta, or the recurrent laryngeal nerve. The tumor also tends to metastasize to the periesophageal lymph nodes and, eventually, to the liver, lungs, or both.

Adenocarcinoma of the esophagus has the fastest growing incidence rate of all cancers in the European countries and United States. The incidence of esophageal carcinoma is approximately 3-6 cases per 100,000 persons, although certain endemic areas appear to have higher per-capita rates.

Until the 1970s, squamous cell carcinoma was the most common type of esophageal cancer (90-95%). It was located in the thoracic esophagus and affected mostly men who had a long history of smoking and alcohol consumption. Over the last 2 decades, the incidence of adenocarcinoma of the distal esophagus and gastroesophageal junction has progressively increased. Currently, it accounts for more than 50% of all new cases of esophageal cancer. Unlike squamous cell carcinoma, it affects mostly white men, and its pathogenesis is linked to gastroesophageal reflux disease (GERD) and the development of Barrett epithelium.

Internationally, Esophageal cancer is the seventh leading cause of cancer death worldwide. Cancer of the esophagus is much more common in some countries. For example, esophageal cancer rates in Iran, northern China, India, and southern Africa are 10 to 100 times higher than in the United States.

Esophageal cancer generally is more common in men than in women, with a male-to-female ratio of 7:1.

The overall 5-year survival rate for esophageal cancer remains approximately 20-25% for all stages.

Chemotherapy with a combination of cytotoxic agents is a common strategy in the treatment of malignant cancers. Although this approach is widely used, toxicity to normal cells combined with low therapeutic indices is an important limitation to its continued use. We at Transgene have developed a strategy that involves the use of monoclonal antibodies to target potent cytotoxic agents to multiple myeloma and esophageal adeno-carcinoma. Here an antibody specific for cell surface antigen is covalently linked to a potent cytotoxic agent used as immuno-conjugate drug. Injected immuno-conjugate drug specifically binds to the cell surface antigen on cancer cells followed by internalization of the antigen-antibody complex to ensure focused delivery and release of the conjugated cytotoxic drug inside the tumor cells, followed by the lysis of the cell.  Immuno-conjugate chemotherapy is a clinically validated strategy, exemplified by gemtuzumab ozogamicin (GO), a humanized anti-CD33 antibody conjugated with the cytotoxic drug calicheamicin and approved for the treatment of relapsed acute myeloid leukaemia. Similar strategy is used for the development of two specific immuno-conjugate cancer drugs, targeting Multiple myeloma and Esophageal adeno-carcinoma. Tumor targeted delivery of the cytotoxic drug not only maximizes its antitumor efficacy but also significantly reduces its exposure to normal tissues, thereby improving its therapeutic index. This strategy of tumor-targeted chemotherapy is therapeutically more advantageous than the traditionally used chemotherapeutic strategy.

The scientists at Transgene have successfully developed humanized monoclonal antibodies and are successful in tagging them to a specific toxin. The drug developed there from has been put through in-vitro and limited animal trials which have confirmed the specific anti-tumor activity of this immuno-conjugate drug in Esophageal Adeno-carcinoma tumor cells, as confirmed not only by remarkable tumor regression but also by the histo-pathology examination.

Transgene has filed patents in the USA specific to the development of an immuno-conjugate drug against Barrett's Esophageal Adenocarcinoma.
 
Transgene plans to undertake pre-clinical trials in Europe during the second half of 2007.