These results show evidence that RTS,S/AS02A maintained protection during the 45-month surveillance period, and they highlight the feasibility of developing an effective vaccine against malaria. In combination with other malaria-control measures, such a vaccine could greatly contribute to reducing the intolerable global burden of this disease. Trial registration. ClinicalTrials.gov identifiers NCT00197041 and NCT00323622 .
BACKGROUND: Regenerative medicine using stem cell technology is an emerging therapy, addressing congenital and acquired diseases. Heterologous Human Adult Liver-derived Progenitor Cells (HHALPCs) have the potency to metabolise ammonium and conjugate bilirubin. Preclinical studies have shown the safety in vitro and in animal models. AIM: We report the safety and preliminary efficacy results of a multicenter phase I/II trial using HHALPCs in pediatric patients with urea cycles disorders (UCD's) or Crigler-Najjar (CN) syndrome METHODS: 14 urea cycle disorder patients and 6 Crigler-Najjar patients were included. Patients were divided in three weight cohort, and three dose levels. A dose escalation from the lowest to the highest dose was applied for the first three patients enrolled in each weight cohort.RESULTS: The safety profile observed was in line with the profile expected for this new cell therapy, the infusion procedure, the concomitant medications, the age group and the underlying disease. Partial left portal vein permanent thrombosis occurred in one patient. Preliminary efficacy data included de novo urea synthesis as demonstrated by the [ 13 C] ureagenesis test at 6 months follow-up versus baseline, engraftment of cells in 3 evaluable patients, and a decrease of bilirubin under similar phototherapy condition in 2 Crigler-Najjar patients.CONCLUSION: This study opens the way for a confirmatory study in a homogeneous cohort of patients with a defined treatment dose.Take-home message: This study reports general safety of Human Adult Liver-derived Progenitor Cells infusion in patients with severe metabolic diseases. Confirmation of efficacy will be addressed in a homogenous cohort of patients with a defined treatment dosis.
The human MAGE3 gene is expressed in a significant proportion of tumors of various histological types, but is silent in normal adult tissues other than testis and placenta. Antigens encoded by MAGE3 may therefore be useful targets for specific antitumor immunization. Two antigenic peptides encoded by the MAGE3 gene have been reported previously. One is presented to cytolytic T lymphocytes (CTL) by HLA-A1, the other by HLA-A2 molecules. Here we show that MAGE3 also codes for a peptide that is presented to CTL by HLA-B44. MAGE3 peptides containing the HLA-B44 peptide binding motif were synthesized. Peptide MEVDPIGHLY, which showed the strongest binding to HLA-B44, was used to stimulate blood T lymphocytes from normal HLA-B44 donors. CTL clones were obtained that recognized not only HLA-B44 cells sensitized with the peptide, but also HLA-B44 tumor cell lines expressing MAGE3. The proportion of metastatic melanomas expressing the MAGE3/HLA-B44 antigen should amount to approximately 17% in the Caucasian population, since 24% of individuals carry the HLA-B44 allele and 76% of these tumors express MAGE3.
We derived lung carcinoma cell lines from tumor material resected from a patient with small-cell lung cancer (SCLC) and from a patient with non-small-cell lung cancer (NSCLC). The patient with NSCLC was vaccinated with irradiated autologous tumor cells. The two patients enjoyed an exceptionally favorable clinical evolution and are currently without signs of cancer 10 and 8 yr after their diagnoses, respectively. Autologous mixed lymphocyte-tumor cell cultures (MLTC) were produced with blood lymphocytes stimulated with irradiated autologous tumor cells. The first patient's SCLC cells, which carried a small amount of human leukocyte antigen (HLA) class I molecules, were incubated with interferon-gamma (IFN-gamma) before being used as stimulator cells. A cytolytic T-lymphocyte (CTL) clone was derived that specifically lysed the IFN-gamma-treated SCLC cells but did not lyse untreated tumor cells or autologous lymphoblasts. Clones of autologous tumor-specific CTL, directed against the NSCLC cells of the other patient, were also obtained. These tumor cells carried a higher level of HLA class I molecules and were lysed by the CTL without incubation with IFN-gamma. Altogether, these results indicate that SCLC and NSCLC cancer cells can be recognized by autologous CTL, and might therefore be susceptible to specific immunotherapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.