81. Tumor cell-based vaccine contributes to local tumor irradiation by eliciting a tumor model-dependent systemic immune responseTinkara Remic, Gregor Serša, Kristina Levpušček, Urša Lampreht Tratar, Katja Uršič Valentinuzzi, Andrej Cör, Urška Kamenšek, 2022, izvirni znanstveni članek Povzetek: Multimodal treatment approaches, such as radio-immunotherapy, necessitate regimen optimization and the investigation of the interactions of different modalities. The aim of this study was two-fold. Firstly, to select the most effective combination of irradiation and the previously developed tumor cell-based vaccine and then to provide insight into the immune response to the selected combinatorial treatment. The study was performed in immunologically different murine tumor models: B16F10 melanoma and CT26 colorectal carcinoma. The most effective combinatorial treatment was selected by comparing three different IR regimens and three different vaccination regimens. We determined the local immune response by investigating immune cell infiltration at the vaccination site and in tumors. Lastly, we determined the systemic immune response by investigating the amount of tumor-specific effector lymphocytes in draining lymph nodes. The selected most effective combinatorial treatment was 5× 5 Gy in combination with concomitant single-dose vaccination (B16F10) or with concomitant multi-dose vaccination (CT26). The combinatorial treatment successfully elicited a local immune response at the vaccination site and in tumors in both tumor models. It also resulted in the highest amount of tumor-specific effector lymphocytes in draining lymph nodes in the B16F10, but not in the CT26 tumor-bearing mice. However, the amount of tumor-specific effector lymphocytes was intrinsically higher in the CT26 than in the B16F10 tumor model. Upon the selection of the most effective combinatorial treatment, we demonstrated that the vaccine elicits an immune response and contributes to the antitumor efficacy of tumor irradiation. However, this interaction is multi-faceted and appears to be dependent on the tumor immunogenicity.
Ključne besede: experimental oncology, multimodal treatment, radio-imunotherapy
Objavljeno v DiRROS: 14.09.2022; Ogledov: 550; Prenosov: 286
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82. Estimating quantitative physiological and morphological tissue parameters of murine tumor models using hyperspectral imaging and optical profilometryTadej Tomanič, Luka Rogelj, Jošt Stergar, Boštjan Markelc, Tim Božič, Simona Kranjc Brezar, Gregor Serša, Matija Milanič, 2022, izvirni znanstveni članek Povzetek: Understanding tumors and their micro-environment are essential for successfuland accurate disease diagnosis. Tissuephysiology and morphology are altered intumors compared to healthy tissues, andthere is a need to monitor tumors and their surrounding tissues, includingblood vessels, non-invasively. This preliminary study utilizes a multimodaloptical imaging system combining hyperspectral imaging (HSI) and three-dimensional (3D) optical profilometry (OP) to capture hyperspectral imagesand surface shapes of subcutaneously grown murine tumor models. Hyper-spectral images are corrected with 3D OP data and analyzed using the inverse-adding doubling (IAD) method to extract tissue properties such as melaninvolume fraction and oxygenation. Blood vessels are segmented using theB-COSFIRE algorithm from oxygenation maps. From 3D OP data, tumor vol-umes are calculated and compared to manual measurements using a verniercaliper. Results show that tumors can be distinguished from healthy tissuebased on most extracted tissue parameters (p<0:05). Furthermore, blood oxy-genation is 50% higher within the blood vessels than in the surrounding tissue,and tumor volumes calculated using 3D OP agree within 26% with manualmeasurements using a vernier caliper. Results suggest that combining HSI andOP could provide relevant quantitative information about tumors and improvethe disease diagnosis.
Ključne besede: medical physics, hyperspectral imaging, diffuse reflectance spectroscopy, blood vessels, tumors
Objavljeno v DiRROS: 08.09.2022; Ogledov: 550; Prenosov: 191
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83. Non-clinical in vitro evaluation of antibiotic resistance gene-free plasmids encoding human or murine IL-12 intended for first-in-human clinical studyŠpela Kos, Maša Omerzel, Tanja Jesenko, Boštjan Markelc, Urška Kamenšek, Katarina Žnidar, Urška Matkovič, Andrej Renčelj, Gregor Serša, Rosana Hudej, Aneja Tuljak, Matjaž Peterka, Maja Čemažar, 2021, izvirni znanstveni članek Povzetek: Interleukin 12 (IL-12) is a key cytokine that mediates antitumor activity of immune cells. To fulfill its clinical potential, the development is focused on localized delivery systems, such as gene electrotransfer, which can provide localized delivery of IL-12 to the tumor microenvironment. Gene electrotransfer of the plasmid encoding human IL-12 is already in clinical trials in USA, demonstrating positive results in the treatment of melanoma patients. To comply with EU regulatory requirements for clinical application, which recommend the use of antibiotic resistance gene-free plasmids, we constructed and developed the production process for the clinical grade quality antibiotic resistance gene-free plasmid encoding human IL-12 (p21-hIL-12-ORT) and its ortholog encoding murine IL-12 (p21-mIL-12-ORT). To demonstrate the suitability of the p21-hIL-12-ORT or p21-mIL-12-ORT plasmid for the first-in-human clinical trial, the biological activity of the expressed transgene, its level of expression and plasmid copy number were determined in vitro in the human squamous cell carcinoma cell line FaDu and the murine colon carcinoma cell line CT26. The results of the non-clinical evaluation in vitro set the basis for further in vivo testing and evaluation of antitumor activity of therapeutic molecules in murine models as well as provide crucial data for further clinical trials of the constructed antibiotic resistance gene-free plasmid in humans.
Ključne besede: interleukin 12, gene electrotransfer, antibiotic resistance, plasmids
Objavljeno v DiRROS: 07.09.2022; Ogledov: 502; Prenosov: 296
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84. Genska terapija v onkologiji, prvi razvojni koraki v SlovenijiMaja Čemažar, Tanja Jesenko, Maša Omerzel, Boštjan Markelc, Urška Kamenšek, Simona Kranjc Brezar, Špela Kos, Urša Lampreht Tratar, Katarina Žnidar, Andrej Renčelj, Urška Matkovič, Teja Valant, Kristina Levpušček, Živa Modic, Tilen Komel, Tim Božič, Urša Kešar, Barbara Starešinič, Katja Uršič Valentinuzzi, Monika Savarin, Primož Strojan, Gorana Gašljević, Maja Ota, Aleš Grošelj, Črt Jamšek, Rosana Hudej, Matjaž Peterka, Franc Smrekar, Barbara Hubad, Marjan Hosta, Jaka Kužnik, Alojz Hosta, Damijan Miklavčič, Matej Reberšek, Aleksandra Cvetkoska, Anja Zajc, Janja Dermol-Černe, Nataša Tozon, Nina Milevoj, Alenka Nemec Svete, Gregor Serša, 2022, strokovni članek Povzetek: Genska terapija postaja čedalje bolj zanimiva tudi v onkologiji. Med aplikacijami je morda najzanimivejša imunostimulacija. Pripravimo lahko plazmidno DNA, ki nosi zapis za različne imunostimulatorne molekule, ki jih vnesemo v celice tumorjev ali normalnih tkiv. Ta tkiva postanejo proizvajalci teh molekul, ki lahko delujejo lokalno ali pa se izločajo tudi sistemsko v krvni obtok. Ker plazmidna DNA ne prehaja celične membrane, so potrebni dostavni sistemi, virusni ali nevirusni. V naših študijah uporabljamo predvsem nevirusni dostavni sistem – elektroporacijo. Interlevkin 12 (IL-12) je eden od zanimivih citokinov, za katerega je znano protitumorsko delovanje s spodbujanjem imunskega odziva in antiangiogenim delovanjem. Namen projekta SmartGene.si je bil pripraviti plazmid z zapisom za interlevkin 12 (plazmid phIL12) in pripraviti vse potrebno za njegovo klinično testiranje za zdravljenje kožnih tumorjev. V konzorciju smo združili moči s partnerji z akademskega in industrijskega področja. Treba je bilo pripraviti plazmid za uporabo v humani onkologiji po zahtevah Evropske agencije za zdravila (EMA). Za prijavo klinične študije na Javno agencijo za zdravila in medicinske pripomočke (JAZMP) smo morali izvesti tudi vse neklinične raziskave o varnosti in učinkovitosti zdravila. Nato je bilo treba razviti postopek priprave zdravila, zagotoviti primerne prostore za pripravo in izvedbo postopka priprave zdravila. V treh letih smo dosegli vse te zastavljene cilje in dobili dovoljenje za izvajanje klinične študije na kožnih tumorjih, ki ga je izdala JAZMP na osnovi pozitivnega mnenja Komisije Republike Slovenije za medicinsko etiko. Zdaj poteka klinična študija faze I preizkušanja plazmida phIL12 na kožnih tumorjih glave in vratu z namenom preveriti varnost in sprejemljivost genskega elektroprenosa plazmida v tumorje. Cilj študije je prav tako določiti primeren odmerek zdravila, ki bi ga v nadaljnji klinični študiji uporabili kot adjuvantno zdravljenje k ablativnim terapijam, kot sta radioterapija ali elektrokemoterapija.
Ključne besede: genska terapija, interlevkin-12, plazmidna DNA, elektroprenos genov, rak kože
Objavljeno v DiRROS: 01.07.2022; Ogledov: 1190; Prenosov: 241
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85. Razvoj avtologne tumorske vakcine pripravljene z obsevanjemTinkara Remic, Gregor Serša, Katja Uršič Valentinuzzi, Kristina Levpušček, Urša Lampreht Tratar, Maja Čemažar, Urška Kamenšek, 2022, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: onkološka cepiva, tumorski antigeni, eksperimentalna onkologija
Objavljeno v DiRROS: 17.06.2022; Ogledov: 649; Prenosov: 189
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86. Vzpostavitev in ovrednotenje radioobčutljivosti HPV-pozitivnega mišjega modela ploščatoceličnega karcinoma ustnega predelaŽiva Modic, Maja Čemažar, Simona Kranjc Brezar, Boštjan Markelc, Gregor Serša, Tanja Jesenko, 2022, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: rak ustnega predela, tumorski modeli, eksperimentalna onkologija
Objavljeno v DiRROS: 17.06.2022; Ogledov: 634; Prenosov: 211
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87. Protitumorska učinkovitost genskega elektroprenosa plazmidne dna z zapisom za rekombinatno protitelo proti CTLA-4 v kombinaciji z obsevanjemBoštjan Markelc, Simona Kranjc Brezar, Tanja Jesenko, Tim Božič, Maja Čemažar, Liesl Jacobs, Kevin Hollevoet, Gregor Serša, 2022, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: obsevanje, genski elektroprenos, eksperimentalna onkologija
Objavljeno v DiRROS: 17.06.2022; Ogledov: 651; Prenosov: 211
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88. Aktivacija cGAS-STING signalne poti po obsevanju humanih tumorskih modelov karcinomov žrelaKristina Levpušček, Simona Kranjc Brezar, Tanja Jesenko, Gregor Serša, Maja Čemažar, Primož Strojan, 2022, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: rak žrela, tumorski modeli, eksperimentalna onkologija
Objavljeno v DiRROS: 17.06.2022; Ogledov: 625; Prenosov: 196
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89. Izločanje dejavnika imunogene celične smrti HMGB1 iz celičnih linij se povečuje z dozo obsevanjaUrša Kešar, Tanja Jesenko, Boštjan Markelc, Katja Uršič Valentinuzzi, Maja Čemažar, Primož Strojan, Gregor Serša, 2022, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: ionizirajoče sevanje, geni, eksperimentalna onkologija
Objavljeno v DiRROS: 17.06.2022; Ogledov: 672; Prenosov: 179
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90. Učinki obsevanja dela tumorja na imunske populacije na tumorskem modelu mišjega karcinoma dojke 4T1Tanja Jesenko, Živa Modic, Tim Božič, Simona Kranjc Brezar, Ilija Vojvodić, Božidar Casar, Ignasi Méndez Carot, Maja Čemažar, Gregor Serša, Boštjan Markelc, 2022, objavljeni povzetek znanstvenega prispevka na konferenci Ključne besede: radioterapija, tumorski modeli, eksperimentalna onkologija
Objavljeno v DiRROS: 17.06.2022; Ogledov: 654; Prenosov: 188
Celotno besedilo (80,61 KB) |
