Browsing by Subject "immunogenicity"

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  • Ehrnrooth, Ninja (Helsingin yliopisto, 2018)
    Allograft hud är kadaverhud som används som ett tillfälligt skydd på det brända och opererade hudområdet. Den tillfälliga allograften vaskulariseras i det rena sårbottnet inom några dagar och stöts bort efter 1-4 veckor. Förvaringen i glycerol dödar cellerna och har antibakteriella och antivirala egenskaper, men man vet inte om allografthudens immunogenicitet minskar om förvaringstiden i glycerol förlängs. Blodtransfusioner och användning av allograft hud är de vanligaste orsakerna till HLA-sensitisering hos brännskadepatienter. I denna avhandling utreder vi allograft hudens immunopositivitet med immunohistokemiska metoder, för att kunna förstå oss bättre på hud allograftens immunogenicitet. Vi vill utreda om lagringstiden i glycerol eller donatorns livslängd ändrar den glycerolförvarade allograftens immuniserande egenskaper. Vi analyserade fem Toll-lika receptorer (TLR2, 4, 5, 7 och 9) och cd45 receptorer i glycerolförvarad allograft hud för att se om det fanns ett samband mellan immunopositiviteten och förvaringstiden i glycerol och donatrons livslängd. Analysen gjordes för att kunna ge direktiv om förvaring och användning av glycerolförvarad allograft hud i hopp om att minska patientens immunisering. Vårt begränsade material minskade på möjligheterna att påvisa de samband, som var målsättningen för studien. Vi fann inte ett samband, men vi kunde se immunopositivitet i allograften, vilket tyder på att det finns proteiner i allograften som kan aktivera immunförsvaret.
  • Garg, Abhishek D.; Galluzzi, Lorenzo; Apetoh, Lionel; Baert, Thais; Birge, Raymond B.; Bravo-San Pedro, Jose Manuel; Breckpot, Karine; Brough, David; Chaurio, Ricardo; Cirone, Mara; Coosemans, An; Coulie, Pierre G.; De Ruysscher, Dirk; Dini, Luciana; de Witte, Peter; Dudek-Peric, Aleksandra M.; Faggioni, Alberto; Fucikova, Jitka; Gaipl, Udo S.; Golab, Jakub; Gougeon, Marie-Lise; Hamblin, Michael R.; Hemminki, Akseli; Herrmann, Martin; Hodge, James W.; Kepp, Oliver; Kroemer, Guido; Krysko, Dmitri V.; Land, Walter G.; Madeo, Frank; Manfredi, Angelo A.; Mattarollo, Stephen R.; Maueroder, Christian; Merendino, Nicolo; Multhoff, Gabriele; Pabst, Thomas; Ricci, Jean-Ehrland; Riganti, Chiara; Romano, Erminia; Rufo, Nicole; Smyth, Mark J.; Sonnemann, Juergen; Spisek, Radek; Stagg, John; Vacchelli, Erika; Vandenabeele, Peter; Vandenberk, Lien; Van den Eynde, Benoit J.; Van Gool, Stefaan; Velotti, Francesca; Zitvogel, Laurence; Agostinis, Patrizia (2015)
    The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall mmunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called "damage-associated molecular patterns" (DAMPs). The emission of DAMPs and other mmunostimulatory factors by cells succumbing to immunogenic cell death (ICD) favors the establishment of a productive interface with the immune system. This results in the elicitation of tumor-targeting immune responses associated with the elimination of residual, treatment-resistant cancer cells, as well as with the establishment of immunological memory. Although ICD has been characterized with increased precision since its discovery, several questions remain to be addressed. Here, we summarize and tabulate the main molecular, immunological, preclinical, and clinical aspects of ICD, in an attempt to capture the essence of this phenomenon, and identify future challenges for this rapidly expanding field of investigation.
  • Ylösmäki, Erkko; Fusciello, Manlio; Martins, Beatriz; Feola, Sara; Hamdan, Firas; Chiaro, Jacopo; Ylösmäki, Leena; Vaughan, Matthew J.; Viitala, Tapani; Kulkarni, Prasad S.; Cerullo, Vincenzo (2021)
    Background Intratumoral BCG therapy, one of the earliest immunotherapies, can lead to infiltration of immune cells into a treated tumor. However, an increase in the number of BCG-induced tumor-specific T cells in the tumor microenvironment could lead to enhanced therapeutic effects. Methods Here, we have developed a novel cancer vaccine platform based on BCG that can broaden BCG-induced immune responses to include tumor antigens. By physically attaching tumor-specific peptides onto the mycobacterial outer membrane, we were able to induce strong systemic and intratumoral T cell-specific immune responses toward the attached tumor antigens. These therapeutic peptides can be efficiently attached to the mycobacterial outer membrane using a poly-lysine sequence N-terminally fused to the tumor-specific peptides. Results Using two mouse models of melanoma and a mouse model of colorectal cancer, we observed that the antitumor immune responses of BCG could be improved by coating the BCG with tumor-specific peptides. In addition, by combining this novel cancer vaccine platform with anti-programmed death 1 (anti-PD-1) immune checkpoint inhibitor (ICI) therapy, the number of responders to anti-PD-1 immunotherapy was markedly increased. Conclusions This study shows that intratumoral BCG immunotherapy can be improved by coating the bacteria with modified tumor-specific peptides. In addition, this improved BCG immunotherapy can be combined with ICI therapy to obtain enhanced tumor growth control. These results warrant clinical testing of this novel cancer vaccine platform.
  • Giannella, Maddalena; Pierrotti, Ligia C.; Helanterä, Ilkka; Manuel, Oriol (2021)
    In response to the COVID-19 pandemic, SARS-CoV-2 vaccines have been developed at an unparalleled speed, with 14 SARS-CoV-2 vaccines currently authorized. Solid-organ transplant (SOT) recipients are at risk for developing a higher rate of COVID-19-related complications and therefore they are at priority for immunization against SARS-CoV-2. Preliminary data suggest that although SARS-CoV-2 vaccines are safe in SOT recipients (with similar rate of adverse events than in the general population), the antibody responses are decreased in this population. Risk factors for poor vaccine immunogenicity include older age, shorter time from transplantation, use of mycophenolate and belatacept, and worse allograft function. SOT recipients should continue to be advised to maintain hand hygiene, use of facemasks, and social distancing after SARS-CoV-2 vaccine. Vaccination of household contacts should be also prioritized. Although highly encouraged for research purposes, systematic assessment in clinical practice of humoral and cellular immune responses after SARS-CoV-2 vaccination is controversial, since correlation between immunological findings and clinical protection from severe COVID-19, and cutoffs for protection are currently unknown in SOT recipients. Alternative immunization schemes, including a booster dose, higher doses, and modulation of immunosuppression during vaccination, need to be assessed in the context of well-designed clinical trials.
  • Li, Yunzhan; Liu, Zehua; Li, Li; Lian, Wenhua; He, Yaohui; Khalil, Elbadry; Makila, Ermei; Zhang, Wenzhong; Torrieri, Giulia; Liu, Xueyan; Su, Jingyi; Xiu, Yuanming; Fontana, Flavia; Salonen, Jarno; Hirvonen, Jouni; Liu, Wen; Zhang, Hongbo; Santos, Hélder A.; Deng, Xianming (2020)
    The analysis of nanoparticles' biocompatibility and immunogenicity is mostly performed under a healthy condition. However, more clinically relevant evaluation conducted under pathological condition is less known. Here, the immunogenicity and bio-nano interactions of porous silicon nanoparticles (PSi NPs) are evaluated in an acute liver inflammation mice model. Interestingly, a new mechanism in which PSi NPs can remit the hepatocellular damage and inflammation activation in a surface dependent manner through protein corona formation, which perturbs the inflammation by capturing the pro-inflammatory signaling proteins that are inordinately excreted or exposed under pathological condition, is found. This signal sequestration further attenuates the nuclear factor kappa B pathway activation and cytokines production from macrophages. Hence, the study proposes a potential mechanism for elucidating the altered immunogenicity of nanomaterials under pathological conditions, which might further offer insights to establish harmonized standards for assessing the biosafety of biomaterials in a disease-specific or personalized manner.
  • Capasso, Cristian; Garofalo, Mariangela; Hirvinen, Mari; Cerullo, Vincenzo (2014)