Since President Nixon declared the war on cancer in 1971, researchers have been executing countless strategies of attack to defeat this cunning and brutal enemy that kills roughly 1,500 people in the United States daily. Alongside the more traditional methods of chemotherapy, radiation therapy, and surgery, vaccines are being developed as possible treatments for the disease.

The National Cancer Institute explains how these vaccines work: cancer vaccines contain pieces of the same antigens that cover the surface of cancer cells. When the vaccine is injected, CD4-positive T lymphocytes, or helper T cells, detect the foreign antigens and trigger the responses of T cells and B cells. B cells produce antibodies, which act by binding to an abnormal cell and inactivating it. In doing so, they help to destroy the abnormal cell. Cytotoxic T cells destroy dangerous cells through chemical means or by triggering apoptosis (cell self-destruction). CVax Magazine adds that when B cells encounter foreign antigens, they not only destroy the cell but also produce memory cells that are duplicates of themselves. In doing so, the immune system builds up a reserve of memory cells such that if the same foreign antigens enter the body again, these immune cells will recognize and destroy the abnormal cells before they proliferate.

Palucka, Ueno, and Banchereau state that studies in breast cancer have provided some of “the most compelling evidence of tumor immunosurveillance in humans.”A study by Pier-Luigi Lollini, a molecular oncologist at the University of Bologna in Italy, tested a vaccine containing HER2/neu, a protein present in many breast tumors. The results of this study showed that in 83-90% of mice injected with the vaccine, no further tumors developed for 52 weeks. The number of preexisting tumors in vaccinated mice was also reduced. Perhaps even more impressively, 30 weeks after being injected with mammary carcinoma cells, 65% of vaccinated mice still did not have tumors. However, it is important to note that the vaccines administered to mice contained levels of recombinant interleukin 12 (rIL-12), which inhibits the growth of blood vessels of tumors, that would exceed maximum tolerance levels for humans, according to the Lollini study.

Mary Disis of the University of Washington, on the other hand, has developed a vaccine suitable for clinical trials. In Disis’ study, thirty-eight participants received a vaccine consisting of peptides from the HER-2/neu protein and granulocyte-macrophage colony-stimulating factor, a white blood cell growth factor, once a month for six months. Of these thirty-eight participants, thirty-one had breast cancer, five had ovarian cancer, and two had non-small-cell lung cancer. It was determined that “the majority of cancer patients who completed all scheduled vaccinations developed both HER-2/neupeptide- and protein-specific T-cell responses.” Furthermore, this immunity “persisted after active immunization had ended.” The promising results of this study are significant in that, as Disis said, “For the first time, clinical trials [of cancer vaccines] are demonstrating anti-tumor efficacy in numbers of patients with cancer, not just one or two unique individuals.”

Vaccines that protect against cervical cancer, such as Gardasil, are already available. However, according to an article on the Newsweek website, these differ from the cancer vaccines that researchers are currently trying to develop in that cervical cancer vaccines aim to protect against cancer-causing viruses, which are not the cause of most cancers.

Other hurdles in the development of cancer vaccines include finding the right type of antigen to target, breaking down tolerance, and avoiding the potential for autoimmune disease. Palucka, Ueno, and Banchereau explain that mutated antigens may be successful in vaccines by taking the approach of triggering immunity, while self-antigens might instead work by “breaking tolerance and inducing autoimmunity.” The authors go on to explain that mutated antigens are advantageous because they “should be recognized as non-self by the immune system” and also have a large store of T cells. However, mutated antigens often must be primed. Additionally, because most cancers are mutated “self-cells,” the immune system often does not detect cancerous cells as dangerous, the authors explain. Thus, as Nature writer Michael Eisenstein explains, another challenge in creating an effective vaccine is to include molecules that “can break this inherent tolerance and turn immunity against these self-proteins—without the nasty effects seen in autoimmune diseases.”

Many attempts to fight cancer, such as chemotherapy and radiation, cause harsh side effects and often weaken the immune system. Now, scientists are trying to use patients’ defense systems to their advantage. By working with the immune system, a successful cancer vaccine could potentially bring not only a decline in the number of existing cancer cases but also the possibility of preventing cancer from the outset.With ample funding and numerous clinical trials underway, researchers are workings towards overcoming the many challenges presented in developing such a vaccine.

References:

^[1] Begley S. Could This Be The End of Cancer? Newsweek. 2011. http://www.thedailybeast.com/newsweek/2011/12/11/could-this-be-the-end-of-cancer.html. Accessed February 15, 2012.

^[1] Cancer Vaccines. National Cancer Institute Fact Sheet.http://www.cancer.gov/cancertopics/factsheet/Therapy/cancer-vaccines/print. Reviewed November 15, 2011. Accessed February 20, 2012.

^[1] How cancer vaccines work: What Is a Vaccine? 2011. http://www.cvax.org/whatis.htm. Accessed February 20, 2012.

^[1]Banchereau J, Palucka K, Ueno H. Recent Development In Cancer Vaccines. J Immunol2011;186;1325-1331. http://www.jimmunol.org/content/186/3/1325.full.pdf. Current as of February 20, 2012. Accessed February 20, 2012.

^[1]AUTHORS.Immunoprevention of HER-2/neu Transgenic Mammary Carcinoma through an Interleukin 12-Engineered Allogeneic Cell Vaccine. Cancer Res June 1, 2004 64; 4001.http://cancerres.aacrjournals.org/content/64/11/4001.full#cited-by. Accessed February 22, 2012.

^[1]NCI Drug Dictionary: recombinant interleukin-12. National Cancer Institute at the National Institutes of Health. http://www.cancer.gov/drugdictionary?cdrid=42153. Accessed February 20, 2012.

^[1]AUTHORS. Generation of T-Cell Immunity to the HER-2/neu Protein After Active Immunization With HER-2/neu Peptide–Based Vaccines.JCO June 1, 2002 vol. 20 no. 11.http://jco.ascopubs.org/content/20/11/2624.full. Accessed February 22, 2012.

^[1] Eisenstein M. Vaccines: Know your enemy.Nature471, S8–S9 (24 March 2011).http://www.nature.com/nature/journal/v471/n7339_supp/full/471S8a.html. Accessed February 22, 2012.