Antibody-based therapy of leukaemia.

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Antibody-based therapy of leukaemia.

JC and TA Waldmann

Expert Rev Mol Med, January 1, 2009; 11: e29.

Over the past decade, monoclonal antibodies have dramatically impacted the

treatment of haematological malignancies, as evidenced by the effect of

rituximab on the response rate and survival of patients with follicular and

diffuse large B cell non-Hodgkin's lymphoma. Currently, only two monoclonal

antibodies - the anti-CD33 immunotoxin gemtuzumab ozogamicin and the

CD52-directed antibody alemtuzumab - are approved for treatment of relapsed

acute myeloid leukaemia in older patients and B cell chronic lymphocytic

leukaemia, respectively. Although not approved for such treatment, alemtuzumab

is also active against T cell prolymphocytic leukaemia, cutaneous T cell

lymphoma and Sézary syndrome, and adult T cell leukaemia and lymphoma. In

addition, rituximab has demonstrated activity against B cell chronic lymphocytic

and hairy cell leukaemia. Monoclonal antibodies targeting CD4, CD19, CD20, CD22,

CD23, CD25, CD45, CD66 and CD122 are now being studied in the clinic for the

treatment of leukaemia. Here, we discuss how these new antibodies have been

engineered to reduce immunogenicity and improve antibody targeting and binding.

Improved interactions with Fc receptors on immune effector cells can enhance

destruction of target cells through antibody-dependent cellular cytotoxicity and

complement-mediated cell lysis. The antibodies can also be armed with cellular

toxins or radionuclides to enhance the destruction of leukaemia cells.

PMID: 19788782

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