How Antibodies Treat Cancer

Monoclonal antibody attacking a blood cancer cell.

Antibodies in the Immune System

The immune system uses both cells and cell products to attack foreign substances in the body. Antibodies, one of the immune system’s most famous cell products, are huge proteins that stick to a microscopic target area, called the antigen. Antibodies are produced by B-lymphocytes, also called plasma cells. Antibodies drift around and circulate in the body. When an antibody comes in close contact with an antigen that it recognizes, it binds, or attaches to the antigen.

Antibodies that are attached to antigens serve somewhat like red flags to other parts of the immune system.

Monoclonal Antibodies

Normally, the immune system generates a huge variety of antibodies that recognize a whole variety of different antigens -- and even different nooks and crannies of the same antigen.

In the laboratory, scientists learned how to take one specific antibody and make many copies of it. The term monoclonal refers to the process of making copies of a single antibody from one clone of cells -- that is, one unique parent cell and its progeny from cell division. Some monoclonal antibodies use genetic engineering to combine parts from different sources into one, new synthesized antibody having characteristics that are desirable for treatment.

Monoclonal Antibodies that Work Alone

Monoclonal antibodies are used together with other anticancer treatments, including chemotherapy, radiation and surgery.

As relates to monoclonal antibodies that "work alone," this refers to such antibodies that are not attached, or conjugated to a poisonous anticancer substance. Monoclonal antibodies that work alone do so by sticking to the cancer cells or something else that is important to the malignant cells' continued well being.

Sometimes they stick directly to the cancer cells and recruit the body’s immune system to seek and destroy. Interestingly, investigators recently reported in the "Journal of Clinical Oncology" that insufficient vitamin D appears to affect how well the anti-cancer therapy rituximab, a monoclonal antibody, does its job. “Vitamin D deficiency is a risk factor for elderly patients with a common B-cell lymphoma treated with R-CHOP,” said investigators. They found evidence that vitamin D deficiency impairs the cancer-cell killing action of rituximab.

Other times, antibodies stick to important structures or proteins, thereby blocking them or "taking them out," so that the cancer cells are adversely impacted. In still other scenarios, they stick to and take out certain checkpoints that serve to dampen or dial down the robust immune response against cancer that is required for success.

Monoclonal Antibodies that Poison Cancer Cells

Monoclonal antibodies can also be designed to stick to antigens on cancer cells and deliver a substance that will kill the cancer cells. In these cases, the antibody is often referred to as a conjugated monoclonal antibody. The antibody still sticks to the cancer cell, like a flagpole stuck in the mud, but the “flag” that cancer researches attach at the top of the pole is something that kills cancer: this can be a chemotherapy drug, a toxin or a radioactive particle, for instance.

Because the chemo or toxic substance is on the antibody, it concentrates the cancer sites, and the idea is that this will lessen the damage to normal cells throughout the body.

Looking for a new approach to treat B-cell malignancies that are refractory to treatment, a group of researchers led by Dr. Daniel Vallera has been developing a targeted approach that uses fragments of antibodies. Using genetic engineering, they made antibodies that bind to CD19 and CD22 on the B-cell cancer cells, but that also have the bacterial diphtheria toxin attached to the antibody. The result is what is known as an immunotoxin, and this one is called DT2219.

The toxins that might be conjugated to an antibody represent a world of research unto themselves. Renowned Rice chemist K.C. Nicolaou recently successfully made a scarce natural marine product that may become a powerful cancer-fighting agent – the molecule shishijimicin A. The substance comes from a rare sea squirt. The group hopes add chemical “handles” so it can be attached to antibodies for delivery to cancer cells.

Immunotoxins are not entirely new, however they are still being actively researched and developed. To date, most success has been achieved treating blood cancers. Obstacles to successful use of immunotoxins on solid tumors include poor penetration into the tumor and the immune response to the toxin component of the therapy. Once a patient mounts an immune response to the toxin, this limits the number of cycles of therapy that can be received.

Sources and Background on Monoclonal Antibodies

Monoclonal antibodies to treat cancer

Rice lab synthesizes cancer-killing compound

Phase I Study of a Bispecific Ligand-Directed Toxin Targeting CD22 and CD19 (DT2219) for Refractory B-cell Malignancies

Modified Immunotoxin as Potential Therapy for Patients With B-cell Malignancies.

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