Oncologists were buzzing about antibody-based drugs like Roche Genentech’s TDM-1 as revolutionary in cancer treatment at the annual meeting of ASCO held in Chicago last week. TDM-1 belongs to a new class of antibody based drugs and are being compared to ‘smart bombs’ that deliver toxins directly into tumor cell with the help of an antibody, without harming healthy cells.
The clinical trial results presented at the conference included 1000 women with breast cancer. TDM-1 was found to delay worsening of breast cancer by 3.2 months and improved progression free median survival to 9.6 months from rate of 6.4 months of using standard therapy. The overall survival rates will be determined in 2014. However, the currently presented data clearly indicated that antibody-drug conjugate was the new technology in cancer drug development.
In addition, ADC treatments allowed patients a better quality of life since it saved them from the toxic effects of chemotherapy medications. With TDM-1, patients did not lose hair. All chemotherapy associated side effects excepting some nausea and muscle cramps vanished.
So, What Are Antibody-Drug Conjugates?
As the name suggests, a monoclonal antibody is linked to a cytotoxic agent/drug using a linker molecule. This makes the antibody lethal to cancer cells. The antibody binds to specific proteins/receptors on surface of cancer cells. The antibody-drug molecule is internalized. Once inside the cell, the antibody molecule disintegrates to release lethal drug. Watch mechanism of action of ADC in the video below.
Antibody-Drug Conjugates on the Anvil
Mylotarg, was the first antibody-drug conjugate to reach market. This was used to treat acute myeloid leukemia. The manufacturer, Pfizer removed the drug from the market after new studies showed that it had safety problems. The toxin fell off the antibody prior to reaching target cancer cells and caused side effects. Current drugs being developed use technology from Seattle Genetics, Bothell, Wash. or ImmunoGen, Waltham Mass. TDM-1 used linker and toxin developed at ImmunoGen.
Some of the new antibody-drug conjugates being developed include:
- Roche Genentech’s TDM-1 presented trial results and have filed for FDA approval.
- Seattle Genetics’ Adcetis was approved in August 2011 for treating Hodgkin’s lymphoma.
- Genentech has over 8 ongoing clinical trials besides TDM-1 and 25 more ADCs in early stages of development.
- Antibodies linked to radioactive isotopes have been approved for treating non-Hodgkin’s lymphoma –
- Bexxar from GlaxoSmithKline
- Zevalin from Spectrum Pharmaceuticals
With antibody-drug conjugate therapy gaining momentum, people suffering from cancer are bound to find relief and be able to stop progression of their tumors.
Video credit: http://www.youtube.com/watch?v=4NH2ldNPeRo
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