Cancer cells are deadly traitors, good cells gone bad. They evade the body’s defense systems, passing themselves off as organisms that pose no threat. But cancer researchers at the University of North Carolina at Chapel Hill’s Eshelman School of Pharmacy are working on a way to blow their cover.

Moo J. Cho, Ph.D., an associate professor of molecular pharmaceutics, is creating a delivery system that would embed bacterial elements in a cancer tumor in order to encourage the body’s immune system to recognize and attack the tumor.

“It’s like planting a big red flag on the tumor to attract the attention of the body’s immune system, which normally ignores cancerous cells,” Cho said. “It’s a great idea. We just don’t know how to do it yet.”

To support his work, Cho, who is also a member of UNC’s Lineberger Comprehensive Cancer Center, has received a five-year grant from the National Cancer Institute worth more than $1.5 million.

The goal of the research is to develop a unique way to intravenously administer a nucleic acid derived from bacteria and deliver it to a tumor. While it is possible to inject some tumors directly, many are relatively inaccessible and can be better reached through the body’s own pathways, Cho said.

The bacteria’s nucleic acid would normally be excreted very rapidly from the body when delivered via IV. Cho plans to add a molecule to the nucleic acid that will allow it to latch on to a class of proteins called IgG immunoglobulin that occur naturally in the body.

“We will ask the IgG antibodies to carry the bacteria-derived nucleic acid as a guest throughout the body,” Cho said. “This will allow the nucleic acid to circulate for days, which is different from how antibodies have been used in classical targeted delivery.”

Cho believes that eventually enough nucleic acid will be carried to the tumor to attract the attention of nearby immune cells, which recognize the nucleic acids as an invading pathogen, triggering an anti-tumor immune response. This approach differs from the classical method of actively targeting a tumor based on specific markers.

“Rapidly growing solid tumors are surrounded by imperfect, almost chaotic, blood flow,” Cho said. “The tissue is very leaky. Because of this unusual permeability, the antibody-nucleic acid complex should become lodged in the tumor periphery. This should mimic a local infection, which the body will work to eliminate.”

Infecting a tumor so that the body can see it and kill it is one element of immunotherapy, a cancer-treatment option that has been used since the late nineteenth century but has fallen out of favor since the development of radiation therapy and chemotherapy. Radiation and chemotherapy are well understood and relatively predictable, but they can kill healthy cells as well as cancerous ones, suppress the immune system, and come with unpleasant and often dangerous side effects.

“You can use a sledgehammer to kill a fly,” Cho said. “But I prefer to try a lighter touch.”

However, getting immunotherapy to be consistently effective has been a challenge to science throughout the years, Cho said. Success or failure varies wildly depending on successfully infecting a tumor and the patient’s reaction to the infectious agent. Cho’s research focuses on the first step of developing a reliable delivery method.

About Cancer

Cancer (medical term: malignant neoplasm) is the general name for a group of more than 100 diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize. Most cancers form a tumor but some, like leukemia, do not. The branch of medicine concerned with the study, diagnosis, treatment, and prevention of cancer is oncology.

Cancer cells can spread to other parts of the body through the blood and lymph systems. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer that begins in basal cells of the skin is called basal cell carcinoma.

Cancer types can be grouped into broader categories. The main categories of cancer include:

• Carcinoma - a cancer which is derived from the lining cells, or epithelium, of an organ. There are 4 major types of epithelium in the body (Glandular, squamous, transitional, and pseudostratified). Some types are only found in a few select organs such as the lung (pseudostratified) or urinary bladder (transitional).  Carcinomas can arise from any of these epithelial types. For example, breast carcinoma is most commonly derived from the lining cells of the milk producing glands. A carcinoma with a glandular growth pattern is an adenocarcinoma.  Common adenocarcinomas include prostate, colon, and breast.  A carcinoma with a growth pattern resembling the squamous lining cells is termed a squamous cell carcinoma.  Common squamous cell carcinomas are found in the esophagus and skin.  However, any of these organs may have either type of carcinoma arising from it, although these latter diagnoses are exceedingly rare.
• Central nervous system cancers - cancers that begin in the tissues of the brain and spinal cord.
• Leukemia - cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of abnormal blood cells to be produced and enter the blood.
• Lymphoma - a cancer derived from the white blood cells that are present in the lymphoid tissues of the body.  These sites most commonly include the lymph nodes and spleen. However, lymphomas may arise from any organ and body site.
• Sarcoma - cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue.

Today, millions of people are living with cancer or have had cancer. The risk of developing most types of cancer can be reduced by changes in a person's lifestyle, for example, by quitting smoking, limiting time in the sun, being physically active, and eating a better diet. Half of all men and one-third of all women in the US will develop cancer during their lifetimes.

Although doctors often cannot explain why one person develops cancer and another does not, research shows that certain risk factors increase the chance that a person will develop cancer. Nearly all cancers are caused by abnormalities in the genetic material of the transformed cells. These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or viruses, bacteria, and certain hormones. Other cancer-promoting genetic abnormalities may be randomly acquired through errors in DNA replication, or are inherited, and thus present in all cells from birth.  Other common risk factors for cancer include:

• Growing Older
• Family history of cancer
• Poor diet, lack of physical activity, or being overweight
• Alcohol