Passive Immunotherapy

       
  Monoclonal Antibodies (mAbs)  
   
     
> Limitations of mAbs  
     
 

 

Passive immunotherapies are comprised of antibodies or other immune system components that are made outside of the body (i.e. in the laboratory) and administered to patients to provide immunity against a disease, to help them fight off an infection, or cancer.

Passive immunotherapies do not stimulate a patient's immune system to "actively" respond to a disease in the way a vaccine does.

MONOCLONAL ANTIBODY THERAPY (mAb)

Monoclonal antibody (mAb) therapy, the most widely used form of cancer immunotherapy today, is a form of passive immunotherapy. Monoclonal antibodies often do not require the patient's immune system to take an active role in fighting the cancer.

Monoclonal antibodies are considered targeted therapy. Targeted immunotherapy is therapy directed to a single target on a cancer cell, usually an antigen or a receptor site on the cancer cell, or it is directed at a cancer specific enzyme or protein.

Monoclonal antibodies bind only to cancer cell-surface specific antigens. When an antibody recognizes the antigen against which it is directed, they fit together like two pieces of a puzzle setting off a cascade of events leading to tumor cell death.

  o Examples of monoclonal antibodies include: Avastin, Erbitux, Rituxan, Herceptin, Mylotarg, Campath, Zevalin, Bexxar, Vectibix, Keytruda, Opdivo, Trecentriq, Imfinzi, Bavencio.  
       
   

Limitations of Monoclonal Antibodies

Despite being the most widely used form of cancer immunotherapy, monoclonal antibodies have not been as successful as expected.

Targeted cancer immunotherapies like monoclonal antibodies were aimed at finding a so called "magic bullet" - a cancer treatment which could destroy only the tumor cells and spare the healthy cells.

Despite the global efforts and more than half a century of work in the fight against cancer, the "magic bullet" has not yet been found. This is perhaps not so surprising considering the complexity of a disease such as cancer. In addition, the products were not always as pure or specific as they initially were thought to be and were generally more toxic when given systemically, especially when given in high doses. 

The major limitations of targeted mAb therapy include:

  o Many mAbs are not administered as first-line therapy: Only a few mAbs are administered as first-line therapy, most are usually administered as a second, third, or last resort cancer treatment when the immune system is already weakened by chemotherapy, surgery and radiation. This may limit their effectiveness.  
       
  o Not all antigens are the same: All of the cells from a specific kind of cancer from the same or different patients may "look" the same when examined microscopically, but they are not. Not all of the cells from patients' cancers may express the antigen against which a specific monoclonal antibody is targeted. In general, only about 30 percent of recipients' cancer cells respond to these "targeted therapies". To optimize this type of therapy, it will be necessary to identify each subgroup of patients with a specific type of cancer cell(s) and develop therapies targeted to, or directed specifically at, their individual cancers. Advances in cancer genetics should result in better selection of a specific treatment and honing of these treatments to each individual patient's cancer.  
       
  o Tumor cells mutate naturally and as a result of chemotherapy and radiation treatment. As a result of these mutations the target antigen on the tumor cell to which the therapy is aimed can change, and the mAbs, which target those specific antigens, could become ineffective.  
       
  o Toxicity associated with some targeted therapies can be significant.