Clinical Applications of Monoclonal Antibodies

Monoclonal Antibodies Approved by FDA for Clinical Use

Most antibodies produced as part of the normal immune response are polyclonal, meaning that they are produced by a number of distinct B lymphocytes, and, as a result, they each have a slightly different specificity for the target antigen (eg, by binding different epitopes or binding the same epitope with different affinities). However, it is possible to produce large quantities of an antibody from a single B-cell clone and when biopharmaceutical companies do this with an eye toward producing a therapeutic, these are called monoclonal antibodies.

Monoclonal antibodies work against cancer in three possible ways

  • Activating the immune system to target malignant cells
  • Supplement the immune system by attaching to the malignant cells and preventing their interaction with growth factor biochemical signaling systems that enable proliferation of cancer.
  • Act as a delivery system to bring a radioactive atom or chemical toxin to the malignant cells.

The first monoclonal antibody used in the clinic was AB 89 against a case of Hodgkin’s lymphoma in 1983.   Below are mABs approved by the FDA for cancer treatment  Dozens of new ones are in clinical trials, both for hematologic malignancies as well as solid tumors.

Immunoglobulin G (IgG) is one of the most abundant proteins in human blood, accounting for about 10–20% of plasma protein. It is the most common protein of the five classes of immunoglobulins in human beings, IgM, IgD, IgG, IgA, and IgE.  IgG has four subclasses numbered IgG1, IgG2, IgG3, and IgG.

Hematologic malignancies:

A number of antigens and their collateral monoclonal antibodies have been identified for the treatment of B cell malignancies. CD20, CD52 and CD22 are targets for B cell malignancies and different forms of chronic lymphocytic leukemia. Each of these antigens plays a role in B and T cell activation, proliferation, and differentiation and hence targeting them attenuates cancer cell growth.

Solid tumors

With solid tumors, cell type specificity becomes an issue as there are not many specific targets for monoclonal antibodies that are not cross-reactive with antigens on normal tissues. Trastuzumab is the most widely used monoclonal antibody against solid tumor in the US.  It has had great success against metastatic breast cancer.

Generic name (trade name) Target Antibody Format Cancer Indication
Unconjugated antibodies      
Rituximab (Rituxan/Mabthera) CD20 Chimeric IgG1 Non-Hodgkin lymphoma
Trastuzumab (Herceptin) HER2 Humanized IgG1 Breast cancer
Alemtuzumab (Campath/MabCampath) CD52 Humanized IgG1 Chronic lymphocytic leukaemia
Cetuximab (Erbitux) EGFR Chimeric IgG1 Colorectal cancer
Bevacizumab (Avastin) VEGFA Humanized IgG1 Colorectal, breast and lung cancer
Panitumumab (Vectibix) EGFR Human IgG2 Colorectal cancer
Ofatumumab (Arzerra) CD20 Human IgG1 Chronic lymphocytic leukemia
Elotuzumab (Empliciti) SLAMF7 blocker: CD 319 Humanized Multiple myeloma
Necitumumab (Portrazza) EGFR Human Non-small-cell lung cancer
Daratumumab (Darzalex) CD38 Human Lymphoma
Dinutuximab (Unituxin)   Chimeric Neuroblastoma
Olaratumab (Lartruvo)   Human Solid tumors
Atezolizumab (Tecentriq)   Humanized Bladder cancer
Immunoconjugates (No radioactive component)      
  CD33 Humanized IgG4 Acute myelogenous leukemia
  CD33 Humanized IgG4 Acute myelogenous leukemia
90Y-Ibritumomab tituxeta (Zevalin) CD20 Mouse Lymphoma
Tositumomab and 131I-tositumomab (Bexxar) CD20 Mouse Lymphoma
Radioimmunotherapy conjugates      
Gemtuzumab ozogamicin (Mylotarg) CD33 Humanized IgG4 Acute myelogenous leukemia
90Y-Ibritumomab tituxeta (Zevalin) CD20 Mouse Lymphoma
Tositumomab and 131I-tositumomab (Bexxar) CD20 Mouse Lymphoma

CD20 = B-lymphocyte antigen CD20 = protein on the surface of B lymphocytes (component of immune system)  CD = Cluster of Differentiation

CD33 = Siglec-3 antigen = protein marker found in bone marrow cells

CD38 = cyclic ADP ribose hydrolase = antigen on surface of some white bloodcells, encoded by the CD38 gene

CD52 = CAMPATH-1 antigen – antigen on surface of some white bloodcells (lymphocutes)

EGFR – epidermal growth factor receptor.  Mutations are evident in many cancers.

HER2 = human epidermal growth factor receptor 2.  Often mutated in breast cancers.

SLAMF7 blocker: CD 319 – signaling lymphocytic activation molecule (SLAM) family – antigen on surface of plasma Myeloma cells

VEGFA – Vascular endothelial growth factor A.  Mutations are evident in many cancers.