Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy

While clinical studies have established that antigen-loaded DC vaccines are safe and promising therapy for tumors 1, their clinical efficacy remains to be ...

NYU Langone Medical Center

Drug metabolizing enzymes participate in the neutralizing of xenobiotics and biotransformation of drugs. Human cytochrome P450, particularly CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5, play an important role in drug metabolism. The genes encoding the CYP enzymes are polymorphic, and extensive data have shown that certain alleles confer reduced enzymatic function. The goal of this study was to determine the frequencies of important allelic variants of CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5 in the Jordanian population and compare them with the frequency in other ethnic groups. Genotyping of CYP1A1(m1 and m2), CYP2C9 (2 and 3), CYP2C19 (2 and 3), CYP3A4 5, CYP3A5 (3 and 6), was carried out on Jordanian subjects. Different variants allele were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). CYP1A1 allele frequencies in 290 subjects were 0.764 for CYP1A1 1, 0.165 for CYP1A1 2A and 0.071 for CYP1A1 2C. CYP2C9 allele frequencies in 263 subjects were 0.797 for CYP2C9 1, 0.135 for CYP2C9 2 and 0.068 for CYP2C9 3. For CYP2C19, the frequencies of the wild type (CYP2C19 1) and the nonfunctional (2 and 3) alleles were 0.877, 0.123 and 0, respectively. Five subjects (3.16 %) were homozygous for 2/2. Regarding CYP3A4 1B, only 12 subjects out of 173 subjects (6.9 %) were heterozygote with none were mutant for this polymorphism. With respect to CYP3A5, 229 were analyzed, frequencies of CYP3A5 1, 3 and 6 were 0.071, 0.925 and 0.0022, respectively. Comparing our data with that obtained in several Caucasian, African-American and Asian populations, Jordanians are most similar to Caucasians with regard to allelic frequencies of the tested variants of CYP1A1, CYP2C9, CYP2C19, CYP3A4 and CYP3A5.

Allele and genotype frequencies of the polymorphic cytochrome P450 genes (CYP1A1, CYP3A4, CYP3A5, CYP2C9 and CYP2C19) in the Jordanian population.

Enzymes du m&eacute;tabolisme des m&eacute;dicaments participent &agrave; la neutralisation des x&eacute;nobiotiques et de biotransformation des m&eacute;dicaments. Human cytochrome P450, particuli&egrave;rement CYP1A1, CYP2C9, CYP2C19, CYP3A4 et CYP3A5, jouent un r&ocirc;le important dans le m&eacute;tabolisme des m&eacute;dicaments. Les g&egrave;nes codant le CYP enzymes sont polymorphes, et grand nombre de donn&eacute;es ont d&eacute;montr&eacute; que certains all&egrave;les conf&eacute;rant r&eacute;duit la fonction enzymatique. L&#39;objectif de cette &eacute;tude &eacute;tait de d&eacute;terminer les fr&eacute;quences de variants all&eacute;liques importants du CYP1A1, CYP2C9, CYP2C19, CYP3A4 et CYP3A5 dans la population jordanienne et de les comparer avec la fr&eacute;quence dans les autres groupes ethniques. G&eacute;notypage des CYP1A1(m1 and m2), CYP2C9 (2 et 3), CYP2C19 (2 et 3), 5 de la CYP3A4, CYP3A5 (3 et 6), a &eacute;t&eacute; r&eacute;alis&eacute;e sur des sujets jordaniens. All&egrave;le diff&eacute;rentes variantes ont &eacute;t&eacute; d&eacute;termin&eacute;es &agrave; l&#39;aide de polym&eacute;rase PCR-RFLP (PCR-RFLP). Fr&eacute;quences all&eacute;liques CYP1A1 dans 290 sujets &eacute;taient 0,764 1 CYP1A1, 0,165 pour 2 a CYP1A1 et 0,071 pour CYP1A1 2C. Fr&eacute;quences all&eacute;liques CYP2C9 dans 263 sujets &eacute;taient 0.797 pour 1 CYP2C9, 0,135 pour 2 CYP2C9 et 0,068 pour 3 CYP2C9. CYP2C19, les fr&eacute;quences de type sauvage (CYP2C19 1) et les all&egrave;les (2 et 3) ne fonctionne pas &eacute;taient 0,877, 0,123 et 0, respectivement. Cinq sujets (3,16 %) &eacute;taient homozygotes pour 2/2. Au sujet de la CYP3A4 1 b, seulement 12 sujets hors 173 sujets (6,9 %) &eacute;taient h&eacute;t&eacute;rozygotes avec aucun mutant pour ce polymorphisme. En ce qui concerne les CYP3A5, 229 ont &eacute;t&eacute; analys&eacute;s, fr&eacute;quences de CYP3A5 1, 3 et 6 ont &eacute;t&eacute; 0,071, 0,925 et 0,0022, respectivement. En comparant nos donn&eacute;es avec celles obtenues dans les populations de plusieurs Caucasiens, les Afro-am&eacute;ricains et les asiatiques, les Jordaniens sont tr&egrave;s semblables aux Caucasiens en ce qui concerne les fr&eacute;quences all&eacute;liques des variantes test&eacute;es du CYP1A1, CYP2C9, CYP2C19, CYP3A4 et CYP3A5.

Fr&eacute;quences all&eacute;liques et g&eacute;notype des g&egrave;nes polymorphes cytochrome P450 (CYP1A1, CYP3A4, CYP3A5, CYP2C9 et CYP2C19) dans la population jordanienne.

Enzimi metabolico droga partecipano la neutralizzazione di xenobiotici e biotrasformazione dei farmaci. Umano citocromo P450, specialmente CYP1A1, CYP2C9, CYP2C19, CYP3A4 e CYP3A5, gioca un ruolo importante nel metabolismo del farmaco. I geni codifica il CYP enzimi sono polimorfici, e numerosi dati hanno dimostrato che alcuni alleli conferiscono ridotta funzione enzimatica. L&#39;obiettivo di questo studio era di determinare le frequenze di importanti varianti allelic di CYP1A1, CYP2C9, CYP2C19 e CYP3A4 e CYP3A5 della popolazione giordana e confrontarli con la frequenza in altri gruppi etnici. Genotipizzazione di CYP1A1(m1 and m2), CYP2C9 (2 e 3), CYP2C19 (2 e 3), 5 CYP3A4, CYP3A5 (3 e 6), &egrave; stata condotta su soggetti Jordanian. Allele diverse varianti sono state determinate mediante polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Frequenze alleliche CYP1A1 nel 290 soggetti erano 0,764 per 1 CYP1A1, 0,165 per 2A CYP1A1 e 0,071 per CYP1A1 C. 2 Frequenze alleliche CYP2C9 in 263 soggetti erano 0.797 per 1 CYP2C9, 0.135 per 2 CYP2C9 e 0,068 per 3 CYP2C9. Per CYP2C19, le frequenze del wild type (1 CYP2C19) e gli alleli non funzionali (2 e 3) erano 0.877, 0.123 e 0, rispettivamente. Cinque soggetti (3.16%) erano omozigoti per 2/2. Per quanto riguarda CYP3A4 1B, solo 12 soggetti fuori 173 soggetti (6,9%) erano eterozigoti con nessuno mutante per questo polimorfismo. Per quanto riguarda CYP3A5, 229 sono stati analizzati, frequenze di CYP3A5 1, 3 e 6 sono stati 0,071, 0,925 e 0.0022, rispettivamente. I nostri dati a confronto con quello ottenuto in popolazioni diverse Caucasico, afro-americani e asiatici, giordani sono pi&ugrave; simili a caucasici per quanto riguarda le frequenze alleliche delle varianti testate del CYP1A1, CYP2C9, CYP2C19 e CYP3A4 e CYP3A5.

Farah Hasan

Cancer Institute

NYU Langone Medical Center

Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy

Farah Hasan

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Cancer Institute

NYU Langone Medical Center

Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy

Cancer Institute