Immunoconjugate

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What is an immunoconjugate? In chemistry, a conjugate is a compound created when you join together two different compounds. An immunoconjugate, therefore, is going to be a compound—or in this case, a treatment, that combines two substances:

-- One is Immune (such as a monoclonal antibody)
-- One is Therapeutic (such as a radionuclde, or isotope)

(Immunoconjugate actually haa a third component, its so-called chemical linker design, vital to the compound's activity but not vital for the patient to know or understand). In short, an immunoconjugate is like taking arming an antibody with the weapons needed to kill a cancer cell.

Immunoconjugate for lymphomas

The field of immunoconjugate is especially small but growing. In this entry we'll take a brief look at the immunoconjugate available or soon t be available in the lymphoma community.

Zevalin

The radioimmunotherapy treatment Zevalin is a classic immunoconjugate: it features an immune component—the monoclonal antibody ibritumomab (along with its chemical linker, tiuxetan), and a therapeutic component, one of two radioactive isotopes (yttrium-90 or indium-111).

This regimen begins with the familiar monoclonal antibody Rituxan. It is then followed by infusions of the radio-labeled ibritumomab. The antibody seeks out CD20+ B-lymphocytes in the body and clings to them long enough to slap the radioactive isotope into the cell and kill it. Zevalin is FDA approved to treat B-cell non-Hodgkin's lymphomas that have experienced previous rituximab-based treatment failure .

Bexxar

Bexxar is another immunoconjugate that uses an immune component—the anti-CD20 monoclonal antibody Tositumomab—and a therapeutic component, iodine-131. This immunoconjugate works in much the same way as Zevalin.

Bexxar is FDA approved to treat relapsed follicular lymphoma that has proven to be rituximab-refractory.

Adcetris

Long known as SGN-35, Seattle Genetics' antibody drug conjugate Adcetris is for relapsed or refractory Hodgkin's lymphoma or anaplastic T-cell lymphoma. It uses an anti-CD30 monoclonal antibody called brentuximab, coupled with the anticancer agent monomethyl auristatin E (aka vedotin), the cytotoxic payload delivered into the cancer cells to kill them.

Adcetris is not yet FDA approved, but that approval is expected in the fall of 2011.

Mylotarg

Between the years 2000 and 2010 another immunoconjugate was on the market, but has since been pulled. Gemtuzumab ozogamicin, marketed as Mylotarg, was designed to treat acute myeloid leukemia but was pulled from the market when it was found to increase patient death without adding any benefit compared to chemotherapy.

Sources

National Cancer Institute, Zevalin
National Cancer Institute, Bexxar
FDA Safety Alert for Mylotarg

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