1. 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, original scientific article Abstract: 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.
Keywords: experimental oncology, multimodal treatment, radio-imunotherapy
Published in DiRROS: 14.09.2022; Views: 125; Downloads: 55
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2. Genska terapija v onkologiji, prvi razvojni koraki v SlovenijiMaja Čemažar, Tanja Jesenko, Maša Bošnjak, 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, professional article Abstract: 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.
Keywords: genska terapija, interlevkin-12, plazmidna DNA, elektroprenos genov, rak kože
Published in DiRROS: 01.07.2022; Views: 338; Downloads: 84
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3. Razvoj avtologne tumorske vakcine pripravljene z obsevanjemTinkara Remic, Gregor Serša, Katja Uršič Valentinuzzi, Kristina Levpušček, Urša Lampreht Tratar, Maja Čemažar, Urška Kamenšek, 2022, published scientific conference contribution abstract Keywords: onkološka cepiva, tumorski antigeni, eksperimentalna onkologija
Published in DiRROS: 17.06.2022; Views: 197; Downloads: 92
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4. 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, published scientific conference contribution abstract Keywords: rak žrela, tumorski modeli, eksperimentalna onkologija
Published in DiRROS: 17.06.2022; Views: 196; Downloads: 83
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5. Priprava in testiranje tumorske vakcine z obsevanjemTinkara Remic, Gregor Serša, Maja Čemažar, Katja Uršič Valentinuzzi, Kristina Levpušček, Urška Kamenšek, 2021, published scientific conference contribution Keywords: genski elektroprenos, obsevanje, tumorska vakcina
Published in DiRROS: 01.04.2022; Views: 249; Downloads: 105
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