Clinical Q & A: What's the latest in vaccine therapy

December 11, 2006

The focus of medicine lies not only in searching for viable treatments and cures for existing ailments but also in the prevention of disease. Vaccination induces immunity after an antigen is introduced to the body. This antigen usually consists of a live attenuated organism, an inactivated organism, a toxoid, or parts of an organism (acellular and subunit). The antigen is incapable of resulting in the full-blown manifestation of the disease, but it is potent enough to generate the formation of antibodies to protect against future illness. Traditionally, vaccination has been used to combat the spread of infectious diseases, such as cholera, rabies, polio, measles, and hepatitis. And this is still the case.

Merck recently brought to market Zostavax (zoster vaccine live, Oka/Merck) and Gardasil (quadrivalent human papillomavirus [types 6, 11, 16, 18] recombinant vaccine). Zostavax is indicated for the prevention of shingles, which is caused by the reactivation of the varicella zoster virus, in people 60 years of age or older. In the Shingles Prevention Study, the overall efficacy of the vaccine in decreasing the risk of developing shingles in this population was 51%. In addition, those who did develop shingles experienced a shorter and less severe form of the disease. Notably, Zostavax is not indicated for the treatment of shingles. Gardasil is indicated for females nine to 26 years of age for the prevention of cervical cancer and genital warts as well as other precancerous or dysplastic lesions caused by human papilloma virus (HPV) types 6, 11, 16, and 18.

The approval of Gardasil marks a significant advancement in women's health, as it is expected to prevent most cases of cervical cancer caused by the HPV strains included in the vaccine. Several clinical studies have demonstrated the vaccine's greater than 90% efficacy rate in protecting against HPV strains 16 and 18, which are responsible for approximately 70% of cervical cancers, and against HPV strains 6 and 11, which, together with strains 16 and 18, cause approximately 90% of reported genital wart infections.

The hepatitis B vaccine and Gardasil protect against infections that could potentially lead to cancer. However, a good deal of energy is now being invested in developing vaccines for patients who already have cancer. Cell Genesys is developing GVAX cancer immunotherapies for the treatment of various cancers. GVAX vaccines are comprised of whole tumor cells that have been manipulated to overexpress and secrete granulocyte macrophage-colony stimulating factor (GM-CSF). GM-CSF is an adjuvant, a substance that activates the immune response to the vaccine. Use of an adjuvant is one strategy utilized by researchers to stimulate an immune response against tumor cells, which are generally not recognized by the immune system as foreign. Cell Genesys is now studying the effect of GVAX immunotherapy on the survival of patients with metastatic hormone refractory prostate cancer in phase III clinical trials. Other GVAX immunotherapies directed against pancreatic cancer and leukemias are also in development.

Patient-specific cancer immunotherapy is in development by Accentia BioPharmaceuticals and Genitope Corp., the manufacturers of Biovaxid and MyVax, respectively. These products are tailored for each specific patient in that the vaccines are made up of a protein, referred to as an idiotype protein, that is unique to a given patient's tumor. The idiotype protein is then linked to an immunogenic protein called keyhole limpet hemocyanin (KLH) and administered with GM-CSF to enhance the immune response. Upon administration, the body recognizes KLH as a foreign substance, and it mounts an immune response against KLH and the idiotype protein as well as all the tumor cells in the body that express the idiotype protein. Thus, the idiotype-KLH combination makes it easier for the body's defense system to distinguish cancerous cells from normal cells and to build an adequate immune response against the tumor cells. Both Biovaxid and MyVax are currently being investigated in phase III trials for the treatment of follicular B-cell non-Hodgkin's lymphoma.