Therapeutic Vaccines for Malignant Brain Tumors

Despite the use of multiple therapies such as surgery and/or radiation, malignant brain tumors (MBTs) often progress and frequently recur after treatment. Even with optimal medical treatment, the rate of recurrence is high in some tumors. For example, only 1 in 20 patients with glioblastoma will live for 3 years or longer after diagnosis and treatment.1 Currently, researchers are developing new biologic therapies that they hope will extend patient survival time and prevent recurrence of MBTs.

Therapeutic cancer vaccines (TCVs) are designed to stimulate the body's natural defenses against cancer. Although many vaccines help protect against future infections or disease, TCVs specifically target existing cancer cells or molecules associated with cancer development and growth. During treatment, patients are inoculated with substances known to elicit a strong immune response against key proteins and other molecules associated with cancer.2 Some of these include tumor-specific antigens (TSAs) and/or tumor-associated antigens (TAAs)—molecules that are present at higher levels in tumor tissue than in normal tissue. In many vaccines, chemicals known as adjuvants are combined with tumor antigens. Adjuvants increase the magnitude and shorten the activation time of the immune response.3 Once activated, the immune system mounts a selective attack on cancer cells that present TSAs or TAAs or on other molecules associated with tumor cell division and growth. TCVs may be administered alone or in combination with surgery, chemotherapy, or radiation therapy.4

Researchers are developing TCVs for numerous cancer indications, and some have shown the ability to elicit a strong immune response toward cancer antigens. However, TCVs for brain cancer face a special challenge. Because of the critical nature of its function and its limited ability to regenerate, the brain is an immune-privileged site (IPS), meaning that it must be protected from potentially dangerous inflammatory immune responses. Part of this protection is provided by the blood-brain barrier, which prevents many substances (including many immune system components) from entering the brain's circulatory system. Therefore, a vaccine that elicits a peripheral immune response may not translate to a therapeutic benefit in the brain. In addition, presentation of antigens from IPS tissues sometimes leads to systemic immune tolerance (decreased immune response toward antigen) as a protective mechanism against inflammation in these critical tissues.

Although some recent clinical trials suggest that TCVs may provide some benefit for patients with MBTs, factors related to the brain's immune privilege might limit the efficacy and usefulness of these vaccines. In addition, clinical trial designs and available data indicate that these TCVs will be used as adjuvant, rather than stand-alone, treatments for MBTs.4 Currently, four companies are conducting...