**5. Vaccines for cancer prevention**

Cancer vaccines have been developed to boost the immune system to fend off cancer. These vaccines or biological response modifiers work by stimulating or restoring the immune system's ability to fight infections and disease. There are two broad types of cancer vaccines: preventive (or prophylactic) vaccines, which are intended to prevent cancer from developing in healthy people; and treatment (or therapeutic) vaccines, which are intended to treat an existing cancer by strengthening the body's natural defenses against the cancer. The FDA has approved two types of vaccines to prevent cancer: vaccines against the hepatitis B virus, which can cause liver cancer, and vaccines against human papillomavirus types 16 and 18, which are responsible for more than 50% of cervical cancer cases (Lehtinen et al. 2011, Wheeler et al. 2011, El-Serag 2011). Furthermore, researchers are developing treatment vaccines against many types of cancer and testing them in clinical trials.

**Table 3** lists the current anti-cancer vaccines either in clinical trial or approved for clinical use. HPV types 16 and/or 18 also cause some vaginal, vulvar, anal, penile, and oropharyngeal cancers (D'Souza et al. 2007, Heard 2011, Wattleworth 2011). The FDA approved vaccines Gardasil and Cervarix protect against HPV 16 and 18 infections which cause cervical cancer (Roden and Wu 2006, Einstein et al. 2009, Saslow et al. 2007). Gardasil is approved for use in females to prevent cervical cancer and some vulvar and vaginal cancers caused by HPV types 16 and 18. It is also approved for use in males and females to prevent anal cancer and precancerous anal lesions caused by these HPV types. Cervarix is approved for use in females ages 10 to 25 to prevent cervical cancer caused by HPV types 16 and 18. All prophylactic vaccines work through the induction of virus-neutralizing antibodies and reduction of the number of cells that are infected after viral infection. This prevents the clinical disease associated with infection. Successful vaccines immunologically mimic the infections they prevent. This primes the adaptive immune system to recall specific effector functions on interaction with the infectious agent in the future. This restimulation process boosts immunity and induces protection against future viral infection. These vaccines are considered to be molecularly targeted because they generate immune responses against specific proteins; that is, the L1 HPV viral capsid protein (for Cervarix and Gardasil) and the hepatitis B surface antigen (for hepatitis B vaccine) (Frederick and Huh 2008, Herzog et al. 2008, Huh, Kendrick and Alvarez 2007, Huh and Roden 2008, Kendrick, Huh and Alvarez 2006, Kirby, Huh and Alvarez 2002, Myers et al. 2008). The HPV vaccines are manufactured from purified L1 structural proteins by recombinant technology. L1 viral capsid proteins are the same protein against which antibodies are made in the natural immune response to HPV. These proteins self-assemble spontaneously to form

inhibitory effects of curcumin are enhanced in the IKK deficient cells, the enzyme required for NF-κB activation (Prakobwong et al. 2011). Thus, curcumin mediates its antiproliferative and apoptotic effects through activation of multiple cell signaling pathways, and thus its anti-tumor activity is under active research. Curcumin blocks a number of targets involved in tumor initiation, promotion, and progression, and is considered a promising chemopreventive agent. Thus, among others, a phase II trial of curcuminoids' effect on cellular proliferation, apoptosis and COX-2 expression in the colorectal mucosa of subjects with recently resected sporadic adenomatous polyps is currently ongoing. Further

Cancer vaccines have been developed to boost the immune system to fend off cancer. These vaccines or biological response modifiers work by stimulating or restoring the immune system's ability to fight infections and disease. There are two broad types of cancer vaccines: preventive (or prophylactic) vaccines, which are intended to prevent cancer from developing in healthy people; and treatment (or therapeutic) vaccines, which are intended to treat an existing cancer by strengthening the body's natural defenses against the cancer. The FDA has approved two types of vaccines to prevent cancer: vaccines against the hepatitis B virus, which can cause liver cancer, and vaccines against human papillomavirus types 16 and 18, which are responsible for more than 50% of cervical cancer cases (Lehtinen et al. 2011, Wheeler et al. 2011, El-Serag 2011). Furthermore, researchers are developing

treatment vaccines against many types of cancer and testing them in clinical trials.

**Table 3** lists the current anti-cancer vaccines either in clinical trial or approved for clinical use. HPV types 16 and/or 18 also cause some vaginal, vulvar, anal, penile, and oropharyngeal cancers (D'Souza et al. 2007, Heard 2011, Wattleworth 2011). The FDA approved vaccines Gardasil and Cervarix protect against HPV 16 and 18 infections which cause cervical cancer (Roden and Wu 2006, Einstein et al. 2009, Saslow et al. 2007). Gardasil is approved for use in females to prevent cervical cancer and some vulvar and vaginal cancers caused by HPV types 16 and 18. It is also approved for use in males and females to prevent anal cancer and precancerous anal lesions caused by these HPV types. Cervarix is approved for use in females ages 10 to 25 to prevent cervical cancer caused by HPV types 16 and 18. All prophylactic vaccines work through the induction of virus-neutralizing antibodies and reduction of the number of cells that are infected after viral infection. This prevents the clinical disease associated with infection. Successful vaccines immunologically mimic the infections they prevent. This primes the adaptive immune system to recall specific effector functions on interaction with the infectious agent in the future. This restimulation process boosts immunity and induces protection against future viral infection. These vaccines are considered to be molecularly targeted because they generate immune responses against specific proteins; that is, the L1 HPV viral capsid protein (for Cervarix and Gardasil) and the hepatitis B surface antigen (for hepatitis B vaccine) (Frederick and Huh 2008, Herzog et al. 2008, Huh, Kendrick and Alvarez 2007, Huh and Roden 2008, Kendrick, Huh and Alvarez 2006, Kirby, Huh and Alvarez 2002, Myers et al. 2008). The HPV vaccines are manufactured from purified L1 structural proteins by recombinant technology. L1 viral capsid proteins are the same protein against which antibodies are made in the natural immune response to HPV. These proteins self-assemble spontaneously to form

research is warranted to evaluate the efficacy of cucumin in other cancers.

**5. Vaccines for cancer prevention** 


Table 3. Preventive and therapeutic cancer vaccines either in clinical trial or approved for clinical use.

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231.

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noninfectious virus-like particles that induce a protective host immune response. Because the virus-like particles contain the same epitopes as naturally occurring HPV, the immune system mounts a primary immune response to the vaccine, enabling a stronger and faster secondary immune response if naturally exposed to the same HPV types (Huh et al. 2007). The difference in the immune response generated by vaccination and natural infection is attributable to high immunogenicity of virus like particles inducing much higher concentrations of neutralizing antibodies to L1. In addition, higher antigen dose in the virus like particles and direct exposure of capsids to systemic immune responses are also observed. One of the challenges in vaccine formulation is balancing immunogenicity and toxicity. Addition of aluminum adjuvants to these vaccines helped to stimulate an immune response by acting as vehicles or immunomodulators. These vehicles transport antigen to lymphoid tissues or cause formation of an antigen depot at the site of injection. Immunomodulators help activate innate and adaptive immunity and increased immunogenicity of the vaccine (Huh et al. 2007, Huh and Roden 2008). The mechanisms by which these vaccines induce protection have not been fully defined but involve cellular immunity and neutralizing immunoglobulin G antibodies. HPV vaccines are designed for prophylactic use only; they do not clear existing HPV infection or treat HPV-related disease. Data from clinical trials utilizing these vaccines suggest that molecular targeting through immunization against infectious agents related to neoplasia is a successful way to prevent or treat early steps of host cell damage that can otherwise lead to cancer.

The FDA has also approved a cancer preventive vaccine that protects against HBV infection. Chronic HBV infection can lead to liver cancer. The original HBV vaccine was approved in 1981, making it the first cancer preventive vaccine to be successfully developed and marketed (Poland and Jacobson 2004). Today, most children in the United States are vaccinated against HBV shortly after birth.
