Milatuzumab (or hLL1) is an anti-CD74 humanized

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...

for the treatment of

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone ...

non-Hodgkin's lymphoma and chronic lymphocytic leukemia. The drug is the first anti-CD74 antibody that has entered into human testing and is currently being studied for the treatment of

. Milatuzumab has received

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

designation from the Food and Drug Administration in the United States for the treatment of

and

chronic lymphocytic leukemia Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow. In CLL, the bone marrow makes too many lymphocytes, which are a type of white blood cell. In patients with CLL, B cell lymphocytes can begin to colle ...

. Milatuzumab was developed b
Immunomedics, Inc
(Morris Plains NJ USA).

CD74

CD74 HLA class II histocompatibility antigen gamma chain also known as HLA-DR antigens-associated invariant chain or CD74 (Cluster of Differentiation 74), is a protein that in humans is encoded by the ''CD74'' gene. The invariant chain (Abbreviated Ii ...

is present on a variety of hematological tumors and even on some solid cancers. It is present in limited amounts in normal tissues but widely found in leukemias, lymphomas and the vast majority of multiple myeloma cases. CD74 is involved in a cell-to-cell communication pathway that is critical for survival. When CD74 is blocked by milatuzumab, it can lead to cell death. CD74 is an attractive target for a drug conjugate because of its rapid internalizing property. In preclinical studies with human lymphomas and myelomas, both naked Milatuzumab and the Milatuzumab conjugated with doxorubicin, an antibody-drug conjugate or ADC, have demonstrated anti-lymphoma activity ''in-vivo.''

Antibody-drug Conjugates

IMMU-110

;hLL1-Dox: Milatuzumab has been linked to

doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toge ...

to form an antibody-drug conjugate or ADC (known as hLL1-Dox or IMMU-110) for treatment of relapsed

. A Phase I/II clinical trial to evaluate this milatuzumab-doxorubicin conjugate began in 2010, but was terminated in 2021 due to lack of efficacy.

References

{{Monoclonals for tumors Monoclonal antibodies Experimental cancer drugs