Biological Therapies for Cancer (Fact Sheet)

What are cancer treatment vaccines?

Cancer treatment vaccines are designed to treat cancers that have already developed rather than to prevent them in the first place. Cancer treatment vaccines contain cancer-associated antigens to enhance the immune system’s response to a patient’s tumor cells. The cancer-associated antigens can be proteins or another type of molecule found on the surface of or inside cancer cells that can stimulate B cells or killer T cells to attack them.

Some vaccines that are under development target antigens that are found on or in many types of cancer cells. These types of cancer vaccines are being tested in clinical trials in patients with a variety of cancers, including prostate, colorectal, lung, breast, and thyroid cancers. Other cancer vaccines target antigens that are unique to a specific cancer type (7-14). Still other vaccines are designed against an antigen specific to one patient’s tumor and need to be customized for each patient. The one cancer treatment vaccine that has received FDA approval, sipuleucel-T, is this type of vaccine.

Because of the limited toxicity seen with cancer vaccines, they are also being tested in clinical trials in combination with other forms of therapy, such as hormonal therapy, chemotherapy, radiation therapy, and targeted therapies. (For more information see Cancer Vaccines.)

What is bacillus Calmette-Guérin therapy?

Bacillus Calmette-Guérin (BCG) was the first biological therapy to be approved by the FDA. It is a weakened form of a live tuberculosis bacterium that does not cause disease in humans. It was first used medically as a vaccine against tuberculosis. When inserted directly into the bladder with a catheter, BCG stimulates a general immune response that is directed not only against the foreign bacterium itself but also against bladder cancer cells. How and why BCG exerts this anticancer effect is not well understood, but the efficacy of the treatment is well documented. Approximately 70 percent of patients with early-stage bladder cancer experience a remission after BCG therapy (15).

BCG is also being studied in the treatment of other types of cancer (16-18).

What is oncolytic virus therapy?

Oncolytic virus therapy is an experimental form of biological therapy that involves the direct destruction of cancer cells. Oncolytic viruses infect both cancer and normal cells, but they have little effect on normal cells. In contrast, they readily replicate, or reproduce, inside cancer cells and ultimately cause the cancer cells to die. Some viruses, such as reovirus, Newcastle disease virus, and mumps virus, are naturally oncolytic, whereas others, including measles virus, adenovirus, and vaccinia virus, can be adapted or modified to replicate efficiently only in cancer cells. In addition, oncolytic viruses can be genetically engineered to preferentially infect and replicate in cancer cells that produce a specific cancer-associated antigen, such as EGFR or HER-2 (19).

One of the challenges in using oncolytic viruses is that they may themselves be destroyed by the patient’s immune system before they have a chance to attack the cancer. Researchers have developed several strategies to overcome this challenge, such as administering a combination of immune-suppressing chemotherapy drugs like cyclophosphamide along with the virus or “cloaking” the virus within a protective envelope. But an immune reaction in the patient may actually have benefits: although it may hamper oncolytic virus therapy at the time of viral delivery, it may enhance cancer cell destruction after the virus has infected the tumor cells (20-23).

No oncolytic virus has been approved for use in the United States, although H101, a modified form of adenovirus, was approved in China in 2006 for the treatment of patients with head and neck cancer. Several oncolytic viruses are currently being tested in clinical trials. Researchers are also investigating whether oncolytic viruses can be combined with other types of cancer therapies or can be used to sensitize patients’ tumors to additional therapy.

What is gene therapy?

Still an experimental form of treatment, gene therapy attempts to introduce genetic material (DNA or RNA) into living cells. Gene therapy is being studied in clinical trials for many types of cancer.

In general, genetic material cannot be inserted directly into a person’s cells. Instead, it is delivered to the cells using a carrier, or “vector.” The vectors most commonly used in gene therapy are viruses, because they have the unique ability to recognize certain cells and insert genetic material into them. Scientists alter these viruses to make them more safe for humans (e.g., by inactivating genes that enable them to reproduce or cause disease) and/or to improve their ability to recognize and enter the target cell. A variety of liposomes (fatty particles) and nanoparticles are also being used as gene therapy vectors, and scientists are investigating methods of targeting these vectors to specific cell types.

Researchers are studying several methods for treating cancer with gene therapy. Some approaches target cancer cells, to destroy them or prevent their growth. Others target healthy cells to enhance their ability to fight cancer. In some cases, researchers remove cells from the patient, treat the cells with the vector in the laboratory, and return the cells to the patient. In others, the vector is given directly to the patient. Some gene therapy approaches being studied are described below.

• Replacing an altered tumor suppressor gene that produces a nonfunctional protein (or no protein) with a normal version of the gene. Because tumor suppressor genes (e.g., TP53) play a role in preventing cancer, restoring the normal function of these genes may inhibit cancer growth or promote cancer regression.

• Introducing genetic material to block the expression of an oncogene whose product promotes tumor growth. Short RNA or DNA molecules with sequences complementary to the gene’s messenger RNA (mRNA) can be packaged into vectors or given to cells directly. These short molecules, called oligonucleotides, can bind to the target mRNA, preventing its translation into protein or even causing its degradation.

• Improving a patient’s immune response to cancer. In one approach, gene therapy is used to introduce cytokine-producing genes into cancer cells to stimulate the immune response to the tumor.

• Inserting genes into cancer cells to make them more sensitive to chemotherapy, radiation therapy, or other treatments

• Inserting genes into healthy blood-forming stem cells to make them more resistant to the side effects of cancer treatments, such as high doses of anticancer drugs

• Introducing “suicide genes” into a patient’s cancer cells. A suicide gene is a gene whose product is able to activate a “pro-drug” (an inactive form of a toxic drug), causing the toxic drug to be produced only in cancer cells in patients given the pro-drug. Normal cells, which do not express the suicide genes, are not affected by the pro-drug.

• Inserting genes to prevent cancer cells from developing new blood vessels (angiogenesis)

Proposed gene therapy clinical trials, or protocols, must be approved by at least two review boards at the researchers’ institution before they can be conducted. Gene therapy protocols must also be approved by the FDA, which regulates all gene therapy products. In addition, gene therapy trials that are funded by the National Institutes of Health must be registered with the NIH Recombinant DNA Advisory Committee.

What is adoptive T-cell transfer therapy?

Adoptive cell transfer is an experimental anticancer therapy that attempts to enhance the natural cancer-fighting ability of a patient’s T cells. In one form of this therapy, researchers first harvest cytotoxic T cells that have invaded a patient’s tumor. They then identify the cells with the greatest antitumor activity and grow large populations of those cells in a laboratory. The patients are then treated to deplete their immune cells, and the laboratory-grown T cells are infused into the patients.

In another, more recently developed form of this therapy, which is also a kind of gene therapy, researchers isolate T cells from a small sample of the patient’s blood. They genetically modify the cells by inserting the gene for a receptor that recognizes an antigen specific to the patient’s cancer cells and grow large numbers of these modified cells in culture. The genetically modified cells are then infused into patients whose immune cells have been depleted. The receptor expressed by the modified T cells allows these cells to attach to antigens on the surface of the tumor cells, which activates the T cells to attack and kill the tumor cells.

Adoptive T-cell transfer was first studied for the treatment of metastatic melanoma because melanomas often cause a substantial immune response, with many tumor-invading cytotoxic T cells. Adoptive cell transfer with genetically modified T cells is also being investigated as a treatment for other solid tumors, as well as for hematologic cancers (24-29).