P-fimbriae vaccines

Protection against acute pyelonephritis was induced by immunization of baboons with purified P-fimbriae ofEscherichia coli as vaccines. To test for cross-protective capacity of two different P-fimbriae vaccines we vaccinated baboons with P-fimbriae purified from eitherE. coli strain ER2 or strain JR1 and subsequently challenged the animals withE. coli strain JR1. All vaccinated animals showed elevated antibody titers to P-fimbriae from both of theE. coli strains used. Both vaccines tended to reduce the time of bacteriuria. They partially prevented pyelonephritis and protected against loss of renal function.     

P-fimbriae receptors in patients with chronic pyelonephritis

The adherence of fluorescein isothiocyanate-labeled P-fimbriated Escherichia coli to uroepithelial cells from 19 women with chronic pyelonephritis was determined with the fluorescence-activated cell sorting technique. The application of this method has made it possible to study bacterial binding to a large number of cells. Renal function was determined in all patients and the recurrences of P-fimbriated Escherichia coli bacteriuria, cystitis and acute pyelonephritis during a 3-year followup were studied. We found a significant correlation between the P-fimbriae receptor accessibility on uroepithelial cells and glomerular filtration rate (r equals -0.75, p less than 0.001). Uroepithelial cells from the patients with chronic pyelonephritis and renal insufficiency had a higher binding capacity of P-fimbriated Escherichia coli than uroepithelial cells from patients with a normal glomerular filtration rate. There was no correlation between kidney function and the availability of P-fimbriae receptors in a control group of patients with polycystic kidney disease.     

Antibody response to P-fimbriae of Escherichia coli in patients with genitourinary infections

The serum antibody response to P-fimbriae of Escherichia coli in patients with genitourinary infections was investigated with enzyme linked immunosorbent assay (ELISA) for P-fimbriae-specific IgG antibody. 1) Female patients with acute pyelonephritis had a significantly (P less than 0.01) higher titer of serum IgG antibody by ELISA, compared with patients with acute cystitis or control subjects. The prevalence of positive serum IgG antibody response was 65% in patients with acute pyelonephritis. 2) Patients with epididymitis with high fever had a significantly (P less than 0.01) higher titer of serum IgG antibody by ELISA, compared with patients with epididymitis without fever or control subjects. The prevalence of positive serum IgG antibody response was 60% in patients with epididymitis with high fever. Therefore, 65% of female patients with acute pyelonephritis and 60% of patients with epididymitis with high fever are infected with P-fimbriated E. coli. The measurement of serum antibody response to P-fimbriae must be helpful for the diagnosis and the antibiotic therapy of epididymitis.     

P-fimbriated Escherichia coli and serum antibody responses to P-fimbriae in pregnant women with urinary tract infections and their children

Escherichia coli (E. coli) is still a major pathogen in urinary tract infections (UTI). It was found that 15 out of 20 cases (75%) of E. coli related UTI were caused by P-fimbriated E. coli, compared to the mere 15% of E. coli isolated from urine and 22% from the stool of healthy controls that were P-fimbriated. All patients studied were pregnant women and their delivered children. Antibody responses to P-fimbriae in the sera of these patients were detected with enzyme-linked immunosorbent assay (ELISA) using purified P-fimbriae. Positive antibody responses were observed at titers of 800-6400 in 8 out of 9 cases of UTI of pregnant women caused by P-fimbriated E. coli. The high level of antibody titers persisted for one month on average and then decreased. These antibodies to P-fimbriae were essentially IgG and transmitted to delivered children from UTI mothers. Therefore, the protective role of these antibodies from P-fimbriated E. coli infections in new born children has been suggested.     

Dendritic-cell tumor vaccines

Most cancers remain incurable. Introduction of novel therapeutic methods, including new cytostatic regimens and targeted therapies, such as monoclonal antibodies and tyrosine kinase inhibitors, have increased remission rates as well as improved patient survival, but the ability to cure many cancer patients remains elusive. It is thus necessary to further develop alternative strategies to improve patient prognosis. The majority of patients who respond to induction therapy inevitably relapse, mainly because of the proliferation of residual malignant cells that have escaped control by induction chemotherapy. Therefore the eradication of minimal residual disease may be crucial to prevent a relapse and achieve a long-term remission. It seems that an advantageous treatment option may be cellular immunotherapy with dendritic-cell vaccines which might induce long-term specific anticancer responses with immune memory cells, which could contribute to effective and lasting elimination of malignant cells.     

Tumor vaccines in renal cell carcinoma

Introduction Although most vaccines target foreign infectious agents, therapeutic cancer vaccines target both well-established and metastatic tumor cells expressing tumor antigens. Active immunotherapy is intended to enhance or activate the immunosurveillance of an individual through a therapeutic vaccine. Renal cell carcinoma (RCC) is one of the most immunoresponsive cancers in humans, which in turn makes it an ideal candidate for immune based therapies. Method Several types of therapeutic vaccines have been tested and applied in the clinical setting and can be divided into cell-based vaccines including direct application of inactivated autologous tumor cells, gene modified tumor cell-based, dendritic cell-based (expressing RCC derived tumor antigens), and non-cell-based vaccines. This review will examine the current status of cell-based vaccine immunotherapy and focuses on non-cell-based vaccine strategies. Conclusion Recent advances in molecular targeting therapy have introduced a battery receptor tyrosine kinase (RTK) and mTOR inhibitors that provide promising treatment options, however, the tolerability of tumor vaccines and the success of clinical effectiveness in selected populations combined with recent advances in cellular therapies warrant the continued exploration of novel methods of tumor vaccine therapies in the clinical setting.     

树突状细胞疫苗在前列腺癌治疗中的应用

目前对于前列腺癌特别是进展期前列腺癌仍然没有十分有效的治疗方法,树突状细胞(DC)疫苗已经渐渐从实验室走向人体临床试验研究,通过将前列腺癌特异性肿瘤抗原导入DC制成的针对前列腺癌的DC疫苗已成功应用于人体,疗效肯定,为前列腺癌的治疗开辟了新的研究领域。本文就前列腺癌DC疫苗的制备及临床应用作一综述。     

Prospects of vaccines against cancer in man.

Preventive immunization is the cheapest and most effective approach to the management of epidemic disease. Certain forms of cancer, including Burkitt's lymphoma, carcinoma of the cervix, primary liver cancer, acute leukaemia and breast cancer show many characteristics of epidemic disease, and the possibility of producing preventive vaccine against these conditions merits serious consideration.     

Immunology and breast cancer: therapeutic cancer vaccines

Cancer immunosurveillance is a process that results from activity of recognition and destruction of cancer cells by innate and adaptive immune effector cells and molecules. Cancer cells can avoid immunosurveillance through the immunoselection, that is the development of poorly immunogenic tumor-cell variants, and through subversion of the immune system (also known as immunosubversion). Identification of tumor antigens (Ags) that can be recognized by immune effector cells has opened the perspective of developing therapeutic vaccines in the field of breast cancer. Breast cancer vaccines can induce immunogenic response against tumors weakly immunogenic; usually have a good tolerance and safety profile and can induce a long-term immune memory, critical to prevent efficiently tumor recurrence. Several studies evaluating breast cancer vaccines have been performed in patients with extended metastatic breast cancer, usually refractory to other standard treatments so that clinical efficacy was difficult to achieve. Significant immune responses against tumor Ags induced upon vaccinations were described to several tumor Ag vaccines. A better understanding of the relation between innate and adaptive immune responses, of the immune escape mechanisms employed by tumor cells and acknowledgment of the importance of both cell-mediated and humoral adaptive immunity for the control of tumor growth are necessary for leading to a more comprehensive immunotherapeutic approach in breast cancer.     

Gene-modified cellular vaccines: technologic aspects and clinical problems

Activity in the cancer vaccine sector has quadrupled in the last decade. A number of therapeutic cancer vaccines are reaching the market. The huge number of clinical trials in progress is expected to undergo evaluation shortly. Whole cell tumor vaccines or gene-modified whole cells are being intensively tested in clinical trials. However, the specificity of the product makes the drug development process, including clinical trials, a considerable challenge. Their complex nature, standardization of manufacturing, and characterization often pose problems. Accordingly, to develop a well characterized controlled vaccine, more than a few factors need to be established. The final cell vaccine formulation must be characterized for product identity, purity, impurities, sterility, potency, cell viability, and total cell number. Therapeutic cancer vaccines show different clinical characteristics than cytotoxic anticancer agents. Unfortunately, the rules of clinical trial design for active immunotherapy have been adapted from the designs for examination of cancer chemotherapy. Accordingly, many research groups and clinical consortia have postulated modifications and unifications of existing clinical trial designs. A clinical development model has suggested that cancer vaccines be investigated in 2 categories of clinical trials: proof-of- principle and efficacy. Moreover, it is becoming clear that no drug demonstrates anticancer activity in all patients. Thus, intensive studies have been performed to seek specific biomarkers which could help stratify patients who are likely to respond to a particular treatment. This presents a big challenge beyond the analysis of the immune system status necessary to assess the effects of active immunotherapy.     

趋化因子在树突状细胞肿瘤疫苗研究中的进展

趋化因子是一类调节免疫细胞定向迁移的细胞因子,其与表达于细胞表面的趋化因子受体结合而发挥生物学功能.树突状细胞(DC)是重要的专职抗原递呈细胞,其主要的应用是制备成各种肿瘤疫苗,树突状细胞功能的行使与趋化因子及其受体介导的细胞迁移密切相关,趋化因子在树突状细胞游走与迁徙过程中始终发挥着调节、促进或抑制的作用,从而促使树突状细胞递呈抗原、激活初始T细胞,引起机体免疫反应,杀伤、消灭肿瘤细胞和炎性分子.     

Dendritic cell vaccines for the treatment of prostate cancer

Advanced prostate cancer remains a disease with few options beyond palliation. Over the past few decades, our understanding of immunology has led to the development of novel therapies for the treatment of many malignancies, including prostate cancer. These generally aim to induce T-cell responses against tumor specific antigens to both reduce tumor mass and potentially avoid relapse. One promising technique is to use autologous dendritic cells, the most potent antigen presenting cell. These can be loaded ex vivo with a given antigen and subsequently injected back into the patient to stimulate the desired effect. Recent trials using these techniques have shown promise in extending survival in patients with prostate cancer. This review will discuss relevant biology behind dendritic cell therapy and highlight the key trials found in the literature.     

Preventive vaccines and immunotherapy clinical trials against cervical cancer

Cervical cancer (CC) is a public health problem among women worldwide, especially in emerging nations. To improve CC control, new adjuvant therapeutic strategies are required. Advances in immunology, genomics and proteomics have accelerated our understanding of the genetic and cellular basis of many cancer types. CC is a member of virus-related neoplasms and its initiation and promotion is associated with persistent infection of oncogenic human papillomavirus. During viral infection and associated-transforming developing lesions, the HPVs co-express non-structural and structural proteins. These early or late proteins are the antigenic target of the immune response. The intervention to stimulate the humoral or cellular immune anti-HPV response is the objective of the immunoprevention and immunotherapy against CC. Recently in a controlled phase III trial of HPV type 16 vaccine using virus-like particles of L1 capsid of HPV-16, the incidence was reduced of both HPV-16 infection and HPV-16-related cervical intraepithelial neoplasia. Although preliminary results of immunotherapy clinical trials against CC did not modify the clinical status, they occasionally show improvement of lymphocyte response against HPV. A recent immunotherapy trial using dendritic cells pulsed with HPV-18 E7 oncoprotein as adjuvant resulted in temporal remission and improved performance status in a patient with metastatic CC. New and different vaccine preventive trials against HPV are being put into practice and clinically tested. It is hoped that in the future it may be possible to eradicate cervical cancer. The success of immunotherapy anti-HPV clinical trials in CC patients will be determined at a future time. The scientific basis for the development of papillomavirus prophylactic and therapeutic vaccines against persistent infection and preinvasive-invasive associated cervical lesions along with the present status of immunopreventive and immunotherapy clinical trials against cervical cancer are commented on in this paper.