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Review of current cancer vaccines

Maria Magdalena Sbenghe , MD Medical Oncology Kimmel Cancer Center Thomas Jefferson University Hospital June 2011. Review of current cancer vaccines . To induce immunity against infectious agents proven to trigger malignancies.

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Review of current cancer vaccines

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  1. Maria Magdalena Sbenghe, MD Medical Oncology Kimmel Cancer Center Thomas Jefferson University Hospital June 2011 Review of current cancer vaccines

  2. To induce immunity against infectious agents proven to trigger malignancies. To induce immunity against cancer cells specific antigens or cell specific antigens excessively expressed on malignant cells. Why using vaccination in cancer? National Cancer Institute

  3. 1. Preventive (or prophylactic) vaccines, which are intended to prevent cancer from developing in healthy people.2. Treatment (or therapeutic) vaccines, which are intended to treat an existing cancer by increasing the immune response to cancer cells. Types of vaccines in cancer National Cancer Institute

  4. Cancer preventive vaccines target infectious agents that cause or contribute to the development of cancer. They work similar with the traditional vaccines. Cancer preventive vaccines- How do they work? National Cancer Institute

  5. Hepatitis B vaccination It was initially approved in 1981. It is the first cancer preventive vaccine. Most children in the USA are vaccinated shortly after birth. The first licensed hepatitis B vaccines were plasma derived and composed of purified HBsAg. Most currently available hepatitis B vaccines are produced by recombinant DNA technology. What cancer preventive vaccines are available in the USA?

  6. Hepatitis B Virus and carcinogenesis Nature Reviews/Cancer

  7. Mechanisms of hepatocarcinogenesis Nature Reviews/Cancer

  8. IMPACT OF HEPATITIS B VACCINATION The major objective of hepatitis B immunization is prevention of chronic infection, which prevents sequelae such as cirrhosis and hepatocellular carcinoma. In the short term, demonstration of a reduction in the HBV-related disease burden relies on indirect measures such as surveillance for acute (symptomatic) hepatitis B and serial cross-sectional seroprevalence studies in populations targeted for vaccination. In the long term, declines in incidence rates and mortality from HBV-related hepatocellular carcinoma can be detected in countries with well-established cancer surveillance systems and registries.

  9. 2. Human papilloma virus vaccination Uses virus like particles (VLP) which correspond to HPV antigens (HPV 6, 11, 16 and 18) There are 2 types of vaccine Gardasil against HPV 6,11, 16 and 18 Cervarix against HPV 16 and 18 Gardasil is approved for use in females for the prevention of cervical cancer, some vulvar and vaginal cancers, caused by HPV types 16 and 18 and for use in males and females for the prevention of genital warts caused by HPV types 6 and 11. The vaccine is approved for these uses in females and males ages 9 to 26. Cervarix is approved for use in females ages 10 to 25 for the prevention of cervical cancer caused by HPV types 16 and 18. What cancer preventive vaccines are available in the USA? National Cancer Institute

  10. Cervical cancer is an important cause of preventable cancer-related death among women. Cervical cancer is the second most common cause of cancer among women worldwide. It primarily affects women between 30 and 45 years of age, thereby representing in an important source of potential years of life lost. HPV 16 and 18 are responsible for approximately 70% of all cervical cancers worldwide (17 other types of HPV are responsible for the rest of 30%). HPV 16 and 18 can also cause vulvar, vaginal, anal, penile and oropharyngeal cancers. Why to vaccinate for HPV? National Cancer Institute

  11. Research, August 28, 2007 • 177(5)

  12. Prophylactic HPV vaccination is highly efficacious in preventing vaccine type specific HPV infection and precancerous cervical disease, particularly among women aged 15–25 years who received all 3 vaccine doses, had no more than 6 lifetime sexual partners and had no prior abnormal results from Pap screening. The per-protocol analyses permit estimation of the effect of vaccinating young girls before becoming sexual active (and thus before HPV exposure) through the use of programs that are able to ensure compliance with the full vaccination schedule. The modified intention-to-treat analyses provide effect estimates that relate to more heterogeneous and potentially less compliant populations. Conclusions of this systematic review Research, August 28, 2007 • 177(5)

  13. This review does not bring evidence that prophylactic vaccination against HPV types 16 and 18 reduces cervical cancer incidence or mortality. The external validity of the results relates to the women included in the studies, who were 15–25 years of age, were mostly white, were mostly from developed nations and were mainly otherwise healthy. Data to help reconcile the gap between the impressive vaccine efficacy demonstrated in these trials and the potential effectiveness of vaccination at reducing the global burden of cervical cancer and death from the disease should be forthcoming from phase IV trials currently underway. Conclusions of this systematic review Research, August 28, 2007 • 177(5)

  14. What about using the vaccine in women older then 25

  15. Women aged 24–45 years with no history of genital warts or cervical disease were enrolled in a randomised, placebo-controlled, double-blind study. Participants were allocated by computer-generated schedule to receive quadrivalent HPV vaccine (n=1911) or placebo (n=1908) at day 1, and months 2 and 6. Coprimary efficacy endpoints were 6 months’ or more duration of infection and cervical and external genital disease due to HPV 6, 11, 16, 18; and due to HPV 16 and 18 alone. Conclusion: The quadrivalent HPV vaccine is efficacious in women aged 24–45 years not infected with the relevant HPV types at enrolment. Lancet 2009; 373: 1949–57

  16. Hepatitis C virus hepatocellular carcinoma Epstein-Barr virus Burkitt lymphoma, non Hodgkin lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma Human T-cell lymphotropic virus (HTLV) 1 acute T-cell leukemia Helicobacter pylori gastric cancer Schistosomahematobium bladder cancer Opisthorchisviverrini cholangiocarcinoma Other infectious agents associated with cancer- but no vaccine available National Cancer Institute

  17. Cancer treatment vaccines are designed to treat cancers that have already developed. They are intended to delay or stop cancer cell growth; to cause tumor regression; to prevent cancer recurrence; eliminate cancer cells that have been left behind by other forms of treatment. Cancer treatment vaccine, how does it work? National Cancer Institute

  18. Cancer cells carry normal self antigens in addition to specific cancer-associated antigens. Cancer cells can undergo genetic changes that may lead to the loss of cancer-associated antigens. Cancer cells can suppress anticancer immune responses by killer T cells by producing inhibitory molecules. Why do the cancer cells escape the immune response? National Cancer Institute

  19. Must stimulate specific immune responses against the correct target. The immune responses must be strong enough to overcome the protective mechanisms of cancer cells against the host immune response. The goals of a cancer treatment vaccine National Cancer Institute

  20. Sipuleucel-T is the first cancer treatment vaccine approved by FDA (April 2010). Indications: metastatic prostate cancer Mechanism: stimulates an immune response to prostatic acid phosphatase(PAP), an antigen present on most prostate cancer cells. Sipuleucel-T increased the survival of men with a certain type of metastatic prostate cancer by 4 months. Cancer treatment vaccines National Cancer Institute

  21. Sipuleucel-T The vaccine is created by isolating immune system cells antigen-presenting cells (APCs) from a patient’s blood through leukapheresis. The APCs are then cultured with PAP-GM-CSF. This complex consist of PAP linked to granulocyte-macrophage colony-stimulating factor (GM-CSF). The GM-CSF protein stimulates the immune system and enhances antigen presentation. Each patient’s cells are then reinfused into the patient. Patients receive three treatments, usually 2 weeks apart, with each round of treatment requiring the same manufacturing process. Although the precise mechanism of action of sipuleucel-T is not known, it appears that the APCs that have taken up PAP-GM-CSF stimulate T cells of the immune system against tumor cells that express PAP. Cancer Treatment Vaccines National Cancer Institute

  22. A phase III study to evaluate the safety and efficacy of sipuleucel-T in a placebo-controlled study. A total of 127 patients with asymptomatic metastatic hormone refractory prostate cancer (HRPC) were randomly assigned in a 2:1 ratio to receive three infusions of sipuleucel-T (n 82) or placebo (n 45) every 2 weeks. Conclusion: While the improvement in the primary end point TTP did not achieve statistical significance, this study suggests that sipuleucel-T may provide a survival advantage to asymptomatic HRPC patients (>4 months survival benefit).

  23. Although big hope has been associated with the use of vaccination in prevention and treatment of cancer, not much progress has been made. Hepatitis B vaccination is the most significant step ahead we have made in cancer vaccination since 1981. In the last 30 years, the second most successful vaccine in cancer prevention is the HPV vaccine which decreased the incidence of pre-cancerous cervical disease and vaccine type specific HPV infection but there is no evidence yet that this reduces cervical cancer incidence and mortality. Sipuleucet-T is the only vaccine approved for cancer treatment in the USA and the survival benefit is 4 months when compared with placebo in patients with asymptomatic, metastatic hormone refractory prostate cancer. Conclusions

  24. Association betwwen HPV infection and oral and oropharyngeal cancer was first proposed in 1983 by Syrjanen et al. HPV associated oropharyngeal cancer seem to have a different prognosis and response to therapy, chemo- and radiotherapy at least in some subsets of patients. How we can use this information to refine the diagnosis and treatment of patients with oropharyngeal cancer is still to be defined. The involvement of HPV in multiple malignancies, oral, oropharyngeal, cervical, anal, penis, vulvar, vaginal cancer inspired the concept of global vaccination against HPV. Dendritic cells, peptide and DNA vaccination continue to be studied in cancer clinical trials. Looking to the future Acknowlegments: Dr. MadhavanPillai, MD, Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University for his guidance in writing this presentation.

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