Clinical responses in women with HPV-16-positive, grade 3 vulvar intraepithelial neoplasia can be achieved by vaccination with a synthetic long-peptide vaccine against the HPV-16 oncoproteins E6 and E7. Complete responses appear to be correlated with induction of HPV-16-specific immunity.

Purpose: The study aims to evaluate the effect of a human papillomavirus type 16 (HPV16) E6 and E7 synthetic long peptides vaccine on the antigen-specificT-cell response in cervical cancer patients. Experimental Design: Patients with resected HPV16-positive cervical cancer were vaccinated with an overlapping set of long peptides comprising the sequences of the HPV16 E6 and E7 oncoproteins emulsified in Montanide ISA-51. HPV16-specificT-cell immune responses were analyzed by evaluating the magnitude, breadth, type, and polarization by proliferation assays, IFNg-ELISPOT, and cytokine production and phenotyped by theT-cell markers CD4, CD8, CD25, and Foxp3. Results: Vaccine-induced T-cell responses against HPV16 E6 and E7 were detected in six of six and five of six patients, respectively.These responses were broad, involved both CD4 + and CD8 Foxp3+ phenotype. Conclusions: The HPV16 E6 and E7 synthetic long peptides vaccine is highly immunogenic, in that it increases the number and activity of HPV16-specific CD4 + and CD8 + Tcells to a broad array of epitopes in all patients. The expansion of CD4 + and CD8 + tumor-specific T cells, both considered to be important in the antitumor response, indicates the immunotherapeutic potential of this vaccine. Notably, part of the vaccine-inducedTcells display a CD4 + CD25 + Foxp3+ phenotype that is frequently associated with regulatory T-cell function, suggesting that strategies to disarm this subset of Tcells should be considered as components of immunotherapeutic modalities against HPV-induced cancers.Cervical cancer is the second most common cancer in women worldwide (1), and it is the first cancer recognized by the WHO to be 100% attributable to the infection with a high-risk type of human papillomavirus (HPV; ref. 2). HPV type 16 (HPV16) is the most common carcinogenic type and is found in around 50% of invasive cervical tumors worldwide (3, 4).

Purpose: To determine the toxicity, safety, and immunogenicity of a human papillomavirus 16 (HPV16) E6 and E7 long peptide vaccine administered to end-stage cervical cancer patients. Experimental Design:Three groups of end-stage cervical cancer patients (in total n = 35) were s.c. vaccinated with HPV16 E6 combined with or separated from HPV16 E7 overlapping long peptides in Montanide ISA-51 adjuvant, four times at 3-week intervals. Group 1 received 300 Ag/ peptide at a single site and group 2 received 100 Ag/peptide of the E6 peptides in one limb and 300 Ag/peptide of the E7 peptides in a second limb. Group 3 received separate injections of E6 and E7 peptides, each at a dose of 50 Ag/peptide. The primary end point was to determine safety and toxicity of the HPV16 long peptides vaccine. In addition, the vaccine-induced T-cell response was assessed by IFNg enzyme-linked immunospot. Results: No toxicity beyond grade 2 was observed during and after four vaccinations. In a few patients, transient flu-like symptoms were observed. Enzyme-linked immunospot analysis of the vaccine-induced immune response revealed that coinjection of the E6 and E7 peptides resulted in a strong and broad T-cell response dominated by immunity against E6. Injection of the E6 and E7 peptides at two different sites increased the E7 response but did not affect the magnitude of the E6-induced immune response. Conclusions: The HPV16 E6 and E7 long peptide-based vaccine is well tolerated and capable of inducing a broad IFNg-associated T-cell response even in end-stage cervical cancer patients.Close to 100% cervical cancers are caused by persistent infection with high-risk human papillomaviruses (HPV; ref. 1). Of the different high-risk HPV types that can cause cervical cancer (2), HPV16 alone is responsible worldwide for more than half of all cases of cervical cancer (1, 2). Genital infection with high-risk HPV is very common and normally cleared within 1 year. However, in a minority (f1%) of the infected individuals, the HPV persists, ultimately resulting in genital neoplastic lesions.Currently, a preventive HPV vaccine is on the market, which effectively prevents this persistent infection and associated disease by the induction of neutralizing antibodies against the envelope proteins of HPV16 and HPV18, the HPV type second on the list of most frequent HPV types associated with cancer. Although these vaccines are very efficient in the prevention of persistent infection by HPV16 and HPV18 (3 -8) and have potential for prevention of cervical intraepithelial neoplasia (9 -11), there is no evidence for efficacy against established .It is generally accepted that virus-infected cells can only be effectively dealt with by cell-mediated adaptive T-cell immunity. Consequently, immunotherapy capable of inducing robust HPV16-specific T-cell immunity is highly desirable for eradication of established HPV16 infection and diseases caused thereby, such as cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, cervical cancer, other anoge...

in terms of LPS and LTA neutralization and lower pro-inflammatory activity. In addition, the acetylated and amidated version of this peptide shows no toxicity and displays higher or equal antimicrobial activity compared to LL-37.

Since the introduction of radioiodinated metaiodobenzylguanidine in 1980, considerable research has been performed, both in the chemical field and in medical sciences. However, despite the wide use of radioiodinated metaiodobenzylguanidine, knowledge about its pharmacology is still limited. This paper reviews the biodistribution and pharmacokinetics, drug interactions, cytotoxicity and dosimetry of radioiodinated metaiodobenzylguanidine. Iodine-131 metaiodobenzylguanidine therapy is in general well tolerated, but its effectiveness needs improvement. Also whole-body dosimetry as part of treatment planning needs to be improved. Future prospects on these items are included in this review.