A pilot clinical trial testing mutant von Hippel-Lindau peptide as a novel immune therapy in metastatic Renal Cell Carcinoma

<p>Abstract</p> <p>Background</p> <p>Due to the lack of specific tumor antigens, the majority of tested cancer vaccines for renal cell carcinoma (RCC) are based on tumor cell lysate. The identification of the <it>von Hippel-Lindau </it>(<it>VHL</it>) gene mutations in RCC patients provided the potential for developing a novel targeted vaccine for RCC. In this pilot study, we tested the feasibility of vaccinating advanced RCC patients with the corresponding mutant VHL peptides.</p> <p>Methods</p> <p>Six patients with advanced RCC and mutated <it>VHL </it>genes were vaccinated with the relevant VHL peptides. Patients were injected with the peptide mixed with Montanide subcutaneously (SQ) every 4 weeks until disease progression or until the utilization of all available peptide stock.</p> <p>Results</p> <p>Four out of five evaluable patients (80%) generated specific immune responses against the corresponding mutant VHL peptides. The vaccine was well tolerated. No grade III or IV toxicities occurred. The median overall survival (OS) and median progression-free survival (PFS) were 30.5 and 6.5 months, respectively.</p> <p>Conclusions</p> <p>The vaccine demonstrated safety and proved efficacy in generating specific immune response to the mutant VHL peptide. Despite the fact that the preparation of these custom-made vaccines is time consuming, the utilization of VHL as a vaccine target presents a promising approach because of the lack of other specific targets for RCC. Accordingly, developing mutant VHL peptides as vaccines for RCC warrants further investigation in larger trials. Trial registration: 98C0139</p

A literature review on the parvovirus B19 infection in sickle cell anemia and β-thalassemia patients

Background: Parvovirus B19 is the causative agent for erythema infectiosum, and also as a potentially life-threatening infectious agent, it is mainly presented in high erythrocyte turnover patients. Sickle cell disease (SCD) is an inherited monogenic hematological disorder resulting from the mutations in the hemoglobin β-chain gene. Thalassemia is a hereditary hematological syndrome that happens in consequence of deficiencies in the production of one or more globin chains. We summarize current knowledge about the prevalence rates of the parvovirus B19 infection in sickle cell anemia and thalassemia patients. Methods: Several online databases were searched including, Scopus, EMBASE, Web of Science, Google Scholar, and PubMed, which were performed amidst 2009�2019 by using distinct keywords: �Thalassemia,� �Parvovirus,� �Anemia,� �Sickle cell anemia,� �parvoviridae,� �parvoviridae infection,� and �parvovirus B19.� Results: Search results indicated 4 and 7 studies for the prevalence of the parvovirus B19 in β-thalassemia and SCD, respectively. Among the β-thalassemia patients, the B19V seroprevalence for IgG and IgM were ranged from 18.2�81 and 14.5�41.1, respectively; meanwhile, B19V DNA positively results was 4�15.3. Moreover, in the SCD group, the extent of B19V IgG was varied from 37.6 to 65.9 and that of IgM was in a range of 2.9�30, and the DNA detection rate was 4�54. Conclusion: B19V seroprevalence changes in several conditions including, different epidemiological features, socio-economic status, and overpopulation. Age can expand the incidence of anti-B19V IgG/IgM in SCD and beta-thalassemia patients. Reinfection and diverse genotypes are relevant factors in the seroprevalence of B19v. The patients� immunological-hematological station and higher abundance of transfusions can affect the B19V seroprevalence in SCD and beta-thalassemia group. Further investigations in this field could be suggested to better understand the virus distribution in this susceptible population of patients. © 2020, The Author(s)