What are cancer vaccines?

Definition

Cancer vaccines are either preventive or therapeutic. Preventive, or prophylactic, vaccines prevent cancer from developing in healthy persons. Therapeutic, or treatment, vaccines treat existing cancer by strengthening the body’s immune response against the malignancy.

Immunotherapy

Vaccines are commonly known for their benefits in preventing
or fighting infectious diseases such as polio, tetanus, or measles. Vaccines, as a
form of immunotherapy, promote immunity, the body’s defense against pathogens and injured
or abnormal cells, such as cancer cells. The immune
system, which can deliver its effector components to different
locations in the body, is such a highly specific system that it can isolate one
cancer cell from a vast amount of other healthy cells and destroy that cancer
cell.

Utilizing basic principles of infectious disease vaccines, a new type of
vaccine is being developed to target one of the most critical public health
concerns: cancer. Although some advances have been made, cancer is
still the leading cause of death in persons younger than age eighty-five years in
the United States.

Cancer is a group of diseases characterized by abnormal and uncontrolled cell
growth, invasion, and sometimes metastasis. In a healthy body, cells
grow, die, and are replaced in a regulated fashion. Damage or change in the
genetic material of cells by internal or environmental factors sometimes results
in immortal cells, which continue to multiply until a mass of cancer cells, or a
tumor, develops. Most cancer-related deaths are caused by
metastasis, in which malignant cells make their way into the bloodstream and
establish colonies in other parts of the body. Cancer immunotherapy manipulates
the immune system to overcome self-tolerance and to recognize cancer cells.

Like the traditional vaccines that present inactivated, attenuated, or subunit
pathogens to the immune system, cancer vaccines present the
right cancer antigen in combination with the right adjuvant to generate
the right type of immune response. This response, whether humoral or cellular, ideally should destroy
the cancer only and leave healthy cells untouched. Cancer cells are different from
normal healthy cells. As such, they are recognized by the immune system as being
different. Proteins expressed by cancer cells are different from normal proteins
or are absent in normal differentiated cells. These proteins can be immunogenic
when presented in the context of a cancer vaccine.

The vaccine is made from cancer-specific proteins or proteins that are found
predominantly in cancer cells. Because of the associated immunologic memory, the
risk of recurrence is reduced compared with traditional treatments. Rather than
compromise the immune system, as many chemotherapy treatments do, cancer
vaccines train the immune system to target those specific malignant cells.
Consequently, some cancer vaccines are safer and do not have the traditional side
effects associated with chemotherapy or radiation therapy. Depending on the
specific vaccine, cancer vaccines might be stand-alone therapies or may be used
with other conventional cancer therapies.

Every cancer, and its vaccine, is different. Personalized medicine is critical to the development of vaccines that must be tailor-made to each person.

Passive and Active Immunotherapy

Cancer vaccines are characterized as either active or passive immunotherapies. While the active type aims to elicit the
host immune system to fight the disease, the passive type does not depend on the
body’s defenses to start the attack. Instead, it uses administered medicines
(antibodies or T cell therapy) to destroy the tumor. Passive
immunotherapy has no immunologic memory associated with the treatment. Any of
these therapies can be targeted to one type of tumor cell or antigen (specific
immunotherapies) or can generally stimulate the immune system (nonspecific
immunotherapies).

Cancer vaccines are either therapeutic or preventive. Therapeutic vaccines treat persons at early stages of the
disease or with minimal residual disease after removal of the main tumor. In some
cases, advanced disease may be treated with a vaccine. Preventive vaccines include the human papillomavirus
(HPV)
vaccine, which can prevent cervical, vaginal, and vulvar
cancers. The hepatitis B virus (HBV) vaccine lowers the risk of developing liver cancer. The
Helicobacter pylori
vaccine targets the bacterium H. pylori, which is
associated with stomach cancer. Hence, the HPV, HBV, and H.
pylori vaccines do not target cancer cells; rather, they are specific
to the viruses or bacteria that give rise to these cancers.

Vaccine Strategies

Cancer vaccines target malignancies such as melanoma, leukemia, and non-Hodgkin’s lymphoma, and cancers of the lung, breast, kidney, ovary, pancreas, prostate, and colorectal area. The unique complex strategies used in cancer vaccine design depend on various considerations particular to the specific cancer process, the optimum level of immunity that can potentially be achieved, and a person’s health status.

In whole cancer-cell vaccines, cancer cells are irradiated before they are returned to the treated person’s body through injection. These vaccines contain thousands of potential antigens expressed in the whole tumor. Antigen vaccines, however, use only one antigen (or a few), whereas peptide vaccines present short fragments of the tumor protein.

Dendritic cell vaccines use specialized antigen-presenting cells that are efficient in presenting tumor antigens and tumor peptides to the immune system. Dendritic cells break down cancer proteins into small fragments and then present these antigens to T cells, thus improving immunologic antigen recognition and, eventually, cancer destruction. Nucleic acid vaccines use the genetic code that codes for cancer protein antigens so that the host cells make the cancer antigen continuously while keeping the immune response stimulated and strong.

Viral and bacterial, vector-based, vaccines can deliver antigens or genes encoding the tumor proteins or peptides to make the host’s immune system more apt to respond. Because bacterial and viral components on these vector vaccines represent pathogen danger signals, they may trigger additional immune responses that might benefit the overall response, making it more robust and longer lasting.

Anti-idiotype vaccines can act passively against B-cell lymphomas or actively by mimicking cancer antigens. In the latter case, these vaccines work through antibody cascades. Some of these vaccines contain adjuvants to amplify either the humoral or the cell-mediated (or both) immune responses to an antigen and break self-tolerance. Adjuvants have been developed to enhance immunogenicity when mixed with proteins, peptides, or deoxyribonucleic acid (DNA).Tumor peptide-MHC (major histocompatibility complex) complexes are important for the recognition of tumor cells by the immune system because tumor peptides are recognized only if they are joined to the MHC complex. Cytotoxic T cells are the killer cells that recognize the peptide-MHC complexes on the tumor cells and destroy the cancer cells.

Impact

Cancer vaccines have the potential to treat cancers in line with treatments
such as surgery or radiation therapy. Cancer vaccines are mostly experimental,
although some have already entered the drug market after receiving U.S.
Food and Drug
Administration approval. Some vaccines have shown promise in
clinical trials, while others have advanced through late-stage clinical
studies.

Using cancer vaccines after the removal of the main tumor by traditional means helps lead the body’s own immune system to destroy any remaining cancer cells and to target metastasis. Immunotherapy has the potential to strengthen the body’s natural defenses, despite cancers that might have already developed, and it can prevent new growth of existing cancers, hamper recurrence of treated cancers, and destroy cancer cells not previously eliminated by other treatments.

When cancer is controlled or cured, cachexia usually stops. During cachexia, there is wasting of adipose and
skeletal muscle. Persons with pancreatic and gastric cancer, for example, suffer
from acute cachexia. Those with cachexia suffer from poor functional performance,
depressed chemotherapy response, and greater mortality. Therefore, the success of
cancer vaccine development may benefit persons with cachexia enormously.

Immunotherapies themselves are costly, but in the long term, they reduce overall medical costs by reducing fees for patient care, management, hospitalization, and death. The pursuit and development of safe and effective cancer vaccines can greatly benefit immunologists, oncologists, molecular biologists, chemists, public health workers, and society in general. Above all, they help persons with cancer.

Bibliography

Finn, O. J. “Cancer Vaccines: Between the Idea and the Reality.” Nature Reviews Immunology 3, no. 8 (2003): 630-641. A review that addresses unique and common challenges to cancer vaccines and the progress that has been made in meeting those challenges.

Jemal, A., et al. “Cancer Statistics, 2010.” CA: A Cancer Journal for Clinicians 60, no. 5 (2010): 277-300. This clinical report examines cancer incidence, mortality, and survival based on incidence data.

Murphy, J. F. “Trends in Cancer Immunotherapy.” Clinical Medicine Insights: Oncology 4 (July 14, 2010): 67-80. Discusses the attempts of cancer immunotherapy to redirect the power and specificity of the immune system toward effectively and safely treating malignancy.

Plotkin, Stanley A., Walter A. Orenstein, and Paul A. Offit. Vaccines. 5th ed. Philadelphia: Saunders/Elsevier, 2008. A comprehensive vaccination textbook covering the topics of development, production, safety and efficacy, morbidity, and mortality.

Raez, L. E., and E. S Santos. “Cancer Vaccines: A New Therapeutic Alternative for Lung Cancer Therapy?” Immunotherapy 1, no. 5 (2009): 727-728. An editorial that discusses challenges for lung cancer vaccine development and clinical activities.

Rosenberg, S. A., J. C. Yang, and N. P. Restifo. “Cancer Immunotherapy: Moving Beyond Current Vaccines.” Nature Medicine 10, no. 9 (2004): 909-915. Review of a cancer vaccine trial that highlights secondary strategies that facilitate cancer regression in preclinical and clinical models.

Schlom, J., P. M. Arlen, and J. L. Gulley. “Cancer Vaccines: Moving Beyond Current Paradigms.” Clinical Cancer Research 13, no. 1 (2007): 3776-3782. Reviews several different cancer-vaccine clinical trials and respective patient response and survival outcomes.

The Scientist.com. “Immune System Versus Cancer.” Available at http://www.the-scientist.com/2009/11/1/36/1. Article that underscores the role of the immune system in cancer within the context of immune surveillance.

Sonpavde, G., et al. “Emerging Vaccine Therapy Approaches for Prostate Cancer.” Reviews in Urology 12, no. 1 (2010): 25-34. Explores different prostate vaccine approaches with selecting proper patient populations, discovering optimal doses, and routes of administration for better outcomes.