Antibody Drug Conjugates: Cancer
One quality synonymous with good
antibodies is their specificity. Some of the best monoclonal antibodies (mAbs)
used in scientific research and disease therapy go through rounds of stringent
selection to ensure that they are highly selective and specific to the target
they bind. Good monoclonal antibodies can be thought of as homing devices, that
will find a target and then specifically bind to that target only, to deliver
the desired therapeutic action.
Imagine combining the specificity
of an antibody with the cytotoxic effect of a cancer drug and what you get is
an Antibody Drug Conjugate (ADC).
ADCs have also been called
“empowered antibodies” or “homing missiles” as they designed to harness the
targeting ability of antibodies while packing a solid punch with delivering
cytotoxic effects through the conjugated drug. Because in ADCs antibodies are
usually conjugated to cytotoxic drugs, they have mostly been used as
anti-cancer drugs. Though theoretically ADCs sound like the ideal candidate to
target specific cancer cells, their development and approval has been fraught
with technical challenges. To date, only four ADCs have been approved as
biopharmaceutical drugs while several others are in the clinical trial
The very first ADC, Gemtuzuman
ozogamicin (Mylotarg), was developed and marketed by wyeth in 2001. Mylotarg
was developed as a monoclonal antibody against CD33 which was linked to a
cytotoxic agent from the class of calicheamicins. CD33 is expressed in most
leukemic blast cells but expression is also specific to normal hematopoietic
cells, although it’s expression deceases as the hematopoietic cells mature. As
most of the leukemic blast cells retain undifferentiated characteristics with
higher expression of CD33 as compared to maturing hematopoetic cells, CD33 was
deemed fit as a candidate to target these leukemic cancer cells.
In United States, ___ was approved
by the FDA in 2001 for use in patients over the age of 60 who are not
considered candidates for standard chemotherapy and/or who had suffered a
relapse with their acute myelogenous leukemia (AML) treatment.