Vaccines against cervical cancer provoke US controversy.
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ABSTRACT:
SUBMITTER: Tanne JH
PROVIDER: S-EPMC1432169 | biostudies-literature | 2006 Apr
REPOSITORIES: biostudies-literature
Publications
Vaccines against cervical cancer provoke US controversy.
BMJ (Clinical research ed.) 20060401 7545
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Project description:Cervical cancer and its precursor intra-epithelial lesions are linked to infection by a subset of so-called "highrisk" human papillomavirus types, which are estimated to infect nearly four hundred million women worldwide. Two prophylactic vaccines have been commercialized recently targeting HPV16 and 18, the most prevalent viral types found in cervical cancer, which operate through induction of capsid-specific neutralizing antibodies. However, in patients with persistent infection these vaccines have not been found to protect against progression to neoplasia. Attempts are being made to develop therapeutic vaccines targeting nonstructural early viral proteins. Among these, E6 and E7 are the preferred targets, since they are essential for induction and maintenance of the malignant phenotype and are constitutively expressed by the transformed epithelial cells. Here are reviewed the most relevant potential vaccines based on HPV early antigens that have shown efficacy in preclinical models and that are being tested in clinical studies, which should determine their therapeutic capacity for eradicating HPV-induced premalignant and malignant lesions and cure cervical cancer.
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Project description:Phase 1 trial of individualized mRNA vaccine for Pancreatic Cancer. We used scRNA-seq to characterize the phenotype of vaccine associated T cells.
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Project description:Human papilloma virus (HPV) is responsible for all cases of cervical cancer. While prophylactic vaccines are available, the development of peptide-based vaccines as a therapeutic strategy is still under investigation. In comparison with the traditional and currently used treatment strategies of chemotherapy and surgery, vaccination against HPV is a promising therapeutic option with fewer side effects. A peptide derived from the HPV-16 E7 protein, called 8Qm, in combination with adjuvants showed promise as a therapeutic vaccine. Here, the ability of polymerized natural amino acids to act as a self-adjuvating delivery system as a therapeutic vaccine was investigated for the first time. Thus, 8Qm was conjugated to polyleucine by standard solid-phase peptide synthesis and self-assembled into nanoparticles or incorporated in liposomes. The liposome bearing the 8Qm conjugate significantly increased mice survival and decreased tumor growth after a single immunization. Further, these liposomes eradicated seven-day-old well-established tumors in mice. Dendritic cell (DC)-targeting moieties were introduced to further enhance vaccine efficacy, and the newly designed liposomal vaccine was tested in mice bearing 11-day-old tumors. Interestingly, these DCs-targeting moieties did not significantly improve vaccine efficacy, whereas the simple liposomal formulation of 8Qm-polyleucine conjugate was still effective in tumor eradication. In summary, a peptide-based anticancer vaccine was developed that stimulated strong cellular immune responses without the help of a classical adjuvant.
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Project description:Human papillomavirus (HPV), particularly type 16, has been associated with more than 99% of cervical cancers. There are two HPV oncogenic proteins, E6 and E7, which play a major role in the induction and maintenance of cellular transformation. Thus, immunotherapy targeting these proteins may be employed for the control of HPV-associated cervical lesions. Although the commercially available preventive HPV vaccines are highly efficient in preventing new HPV infection, they do not have therapeutic effects against established HPV infection or HPV-associated lesions. Since T cell-mediated immunity is important for treating established HPV infections and HPV-associated lesions, therapeutic HPV vaccine should aim at generating potent E6 and E7-specific T cell-mediated immune responses. DNA vaccines have now developed into a promising approach for antigen-specific T cell-mediated immunotherapy to combat infection and cancer. Because dendritic cells are the most potent professional antigen-presenting cells, and are highly effective in priming antigen-specific T cells, several DNA vaccines have employed innovative strategies to modify the properties of dendritic cells (DCs) for the enhancement of the DNA vaccine potency. These studies have revealed impressive pre-clinical data that has led to several ongoing HPV DNA vaccine clinical trials.
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Project description:There is a paucity of data on trust of service users in cervical screening. A significant controversy in Ireland's national cervical cancer screening programme emerged in 2018. The Health Service Executive (HSE) confirmed that a clinical audit had revealed that more than 200 women who developed cancer had not been told of earlier misdiagnosed smear tests. During this high profile controversy we conducted qualitative interviews exploring factors that influence cervical screening participation. Women who had been invited for routine screening tests were recruited from the national screening register. Telephone interviews were conducted with 48 women aged 25-65 years; with a range of screening histories - 34 were adequately screened (attended all routine screening tests) and 14 were inadequately screened (attended some/no screening tests). Thematic analysis was conducted and all interviewees spontaneously raised the screening controversy revealing that the crisis had resulted in serious loss of trust, faith and confidence in the screening programme. Publicity surrounding the controversy had some beneficial effects, including increased awareness of the value of screening and beliefs that intense focus on the programme will improve the service long-term. Strategies which incorporate these findings could help rebuild trust in screening.
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Project description:Cervical cancer continues to cause significant morbidity and mortality worldwide, making prophylactic cervical cancer vaccines an important focus for cervical cancer prevention. The increasing accessibility of these vaccines worldwide has the potential to greatly decrease the incidence and burden of disease in the future. However, current prophylactic vaccines offer no therapeutic benefit for persons already infected with human papillomavirus HPV types targeted by vaccines or persons with precancerous lesions or cervical cancer. The protection offered by current vaccines is primarily against HPV types used to derive the vaccine, although partial cross-protection for related virus types has been observed. Herein, we describe findings from preclinical and clinical studies that employ vaccine strategies that have the potential to shape the future of vaccines against cervical cancer. Modalities include prophylactic strategies to target more oncogenic virus types by using the minor capsid antigen L2 and/or by increasing the number of types used to derive virus-like particle vaccines. Therapeutic strategies include the development of vaccines against HPV early proteins (targets for cellular immunity) for the resolution of precancerous lesions and cervical cancer. Future applications of existing virus-like particle-based vaccines are also discussed.
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Project description:Vaccines used to prevent infections have long been known to stimulate immune responses to cancer as illustrated by the approval of the Bacillus Calmette-Guérin (BCG) vaccine to treat bladder cancer since the 1970s. The recent approval of immunotherapies has rejuvenated this research area with reports of anti-tumor responses with existing infectious diseases vaccines used as such, either alone or in combination with immune checkpoint inhibitors. Here, we have reviewed and summarized research activities using approved vaccines to treat cancer. Data supporting a cancer therapeutic use was found for 16 vaccines. For 10 (BCG, diphtheria, tetanus, human papillomavirus, influenza, measles, pneumococcus, smallpox, typhoid and varicella-zoster), clinical trials have been conducted or are ongoing. Within the remaining 6, preclinical evidence supports further evaluation of the rotavirus, yellow fever and pertussis vaccine in carefully designed clinical trials. The mechanistic evidence for the cholera vaccine, combined with the observational data in colorectal cancer, is also supportive of clinical translation. There is limited data for the hepatitis B and mumps vaccine (without measles vaccine). Four findings are worth highlighting: the superiority of intravesical typhoid vaccine instillations over BCG in a preclinical bladder cancer model, which is now the subject of a phase I trial; the perioperative use of the influenza vaccine to limit and prevent the natural killer cell dysfunction induced by cancer surgery; objective responses following intratumoral injections of measles vaccine in cutaneous T-cell lymphoma; objective responses induced by human papillomavirus vaccine in cutaneous squamous cell carcinoma. All vaccines are intended to induce or improve an anti-tumor (immune) response. In addition to the biological and immunological mechanisms that vary between vaccines, the mode of administration and sequence with other (immuno-)therapies warrant more attention in future research.
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Project description:With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented.
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