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Inflammation and Infection
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Judith Hall, Christopher K. Harding
Genetic susceptibility factors:TLR polymorphisms are linked to adult UTI susceptibility.TLR5 polymorphism encoding a receptor variant that restricts flagellin-induced host signalling responses is associated with an increased risk of recurrent UTI in women.HLA-A3 antigen associated with four times more risk of recurrent UTI.ABO group antigen non-secretors, Lewis non-secretor, and P blood group secretors.
Major histocompatibility complex
Published in Gabriel Virella, Medical Immunology, 2019
Ellen Klohe, Janardan P. Pandey
Hemochromatosis is a disorder that increases the risk of iron overload. Family studies in Caucasians of western European descent demonstrated autosomal recessive inheritance in linkage with HLA-A3. Decades later, the HFE gene was discovered in close proximity to HLA-A. A common mutation within the HFE gene prohibits β2-microglobulin from binding to the HFE α-chain. This disrupts the binding of HFE to the transferrin receptor and alters iron absorption pathways.
Prospects for a personalized peptide vaccine against lung cancer
Published in Expert Review of Vaccines, 2019
Yoshiro Nakahara, Taku Kouro, Yuka Igarashi, Mamoru Kawahara, Tetsuro Sasada
Yamada et al. reported a feasibility study of PPV for patients with advanced NSCLC who failed at least two regimens [43]. In this study, patients positive for HLA-A2, HLA-A24, HLA-A26, or HLA-A3 supertypes (HLA-A3, HLA-A11, HLA-A31, or HLA-A33) were enrolled. Thirty-one peptides were employed for vaccination (12 peptides for HLA-A2, 16 peptides for HLA-A24, 4 peptides for HLA-A26, and 9 peptides for HLA-A3 supertypes) as reported previously. A maximum of four HLA-matched peptides showing higher peptide-specific IgG titers in plasma before vaccination were selected from 31 pooled peptide candidates. Among 57 patients enrolled, 23 patients received PPV with chemotherapy, 16 patients received PPV with molecular-targeted therapy, and 18 patients received PPV alone. No severe adverse effects related to PPV were observed. The median overall survival (OS) in the PPV/chemotherapy group, PPV/molecular-targeted therapy group, and PPV group were 22.8, 15.4, and 7.4 months, respectively. CTL responses to the vaccinated peptides became detectable after vaccination in 58%, 50%, and 42% of the patients in each of the three groups, respectively. In contrast, peptide-specific IgG responses after vaccination increased in 55%, 75%, and 62% of the patients in each of the three groups, respectively. Interestingly, median OS in the patients with CTL responses tended to be longer than that without CTL responses. In addition, the patients with increased IgG responses to non-vaccinated HLA-matched peptides, which might be a result of epitope spreading, tended to show better clinical responses, compared to those without. These results suggested the feasibility and promising clinical efficacy of PPV for patients heavily treated for NSCLC.
In situ delivery of allogeneic natural killer cell (NK) combined with Cetuximab in liver metastases of gastrointestinal carcinoma: A phase I clinical trial
Published in OncoImmunology, 2018
O. Adotevi, Y. Godet, J. Galaine, Z. Lakkis, I. Idirene, J. M. Certoux, M. Jary, R. Loyon, C. Laheurte, S. Kim, A. Dormoy, F. Pouthier, C. Barisien, F. Fein, P. Tiberghien, X. Pivot, S. Valmary-Degano, C. Ferrand, P. Morel, E. Delabrousse, C. Borg
Donor identification was performed among patients’ relative in a first step. In the absence of familial donor, selection was performed among healthy blood donors from the French Blood Bank (EFS, Bourgogne Franche-Comté). At least one KIRL (Killer Immunoglobulin Receptor Ligand) mismatch was required. MHC class I alleles considered for donor selection were HLA A3-A11, HLA-Cw or HLA Bw4. A two digits HLA genotyping assay was used to determine donor and patient HLA A3-A11, Cw or Bw4 status. High-resolution genotyping was performed to confirm HLA allelic expression.
Targeted agents for HER2-positive breast cancer in older adults: current and future perspectives
Published in Expert Opinion on Investigational Drugs, 2018
Enrique Soto-Perez-De-Celis, Kah Poh Loh, Capucine Baldini, Nicolò Matteo Luca Battisti, Yanin Chavarri-Guerra, Nienke A. De Glas, Tina Hsu, Arti Hurria
NeuVax™ is the most studied vaccine against the HER2 protein. It is composed by the HER2-derived peptide E75 (nelipepimut-S) combined with the immune-adjuvant granulocyte macrophage colony-stimulating factor (GM-CSF) and induces CD8+ and CD4+ Th1 responses against HER2 [95]. One of the limitations of treatment development with E75 vaccines is its restriction to HLA-A2 and HLA–A3 subtypes [96]. In the adjuvant setting, a phase I/II study enrolled node-positive and high-risk node-negative patients with tumors expressing any degree of HER2. HLA-A2/3+ patients (n = 108) were vaccinated, while HLA-A2/3-negative patients (n = 79) were followed prospectively as controls. The median age of patients in the vaccination arm was 57 years (range 28–78). Five-year DFS was 89.7% in the vaccinated group versus 80.2% in controls (p = 0.08), giving a 48% reduction in the relative risk of recurrence [97]. The vaccine caused mainly local toxicities, most commonly injection site erythema and pruritus, all grade 1 (83.3%) and grade 2 (16.7%). Systemic toxicities, such as bone pain, influenza-like symptoms, and fatigue, were mild. Unfortunately, a RCT (PRESENT, NCT01479244) of NeuVax™ in early-stage BC was stopped early due to futility, although results have not been published. Two additional studies are ongoing in combination with trastuzumab: a phase IIb trial in node-positive (or HR negative, node negative) patients with HER2+ BC (NCT01570036); and a phase II trial in patients with high-risk node-positive or -negative HER2+ tumors (NCT02297698). Other vaccines currently under development are summarized in Figure 4. Age-specific analyses will be relevant to understand if anti-HER2 vaccines can generate an efficacious antibody response in the context of the aging immune system of older adults, who may have a decline in adaptive immunity and in vaccine longevity [98].