Anna Pasetto

• Mensali, Nadia; Joaquina, Sandy Roxane; Montlaur, Constance De; Casey, Nicholas Paul; Nesset, Thomas Olsen & Myklebost, Ola [Show all 12 contributors for this article] (2026). Pre-clinical validation of OSCAR-3 mRNA-based CAR T cells for targeting osteosarcomas. Cytotherapy. ISSN 1465-3249. 28(12). doi: 10.1016/j.jcyt.2026.102930. Full text in Research Archive Show summary

  Background aims: Osteosarcoma (OS) is a rare cancer affecting children and young adults with a good prognosis when localized. Nevertheless, primary metastases or metastatic relapses are associated with high mortality, underlying the need for novel treatment strategies. Immunotherapy, and more recently Chimeric antigen receptor (CAR)-based therapy, is being investigated as a new approach for the management of solid tumors, although clinical results in OS have so far been limited. Methods: We developed a second-generation CAR (OSCAR-3), derived from the TP-3 hybridoma and targeting ALPL-1, an isoform of alkaline phosphatase selectively expressed in OS. Results: Stable OSCAR-3 expression in T cells demonstrated potent anti-tumor activity in pre-clinical models. To enable safer clinical translation, we further engineered OSCAR-3 as an mRNA-based CAR. OSCAR-3 mRNA CAR T cells maintained cytotoxic activity in vitro and in vivo, and, importantly, delayed tumor progression in OS patient-derived xenograft models. Conclusions: These findings support the further development of OSCAR-3 mRNA CAR T cells as a strategic approach that prioritizes safety over persistence for first-in-human studies, while preserving the ability to reduce tumor growth.

• Mazzotti, Lucia; Souza, Patricia Borges de; Azzali, Irene; Angeli, Davide; Nanni, Oriana & Sambri, Vittorio [Show all 17 contributors for this article] (2025). Exploring the Relationship Between Humoral and Cellular T Cell Responses Against SARS-CoV-2 in Exposed Individuals From Emilia Romagna Region and COVID-19 Severity. HLA. ISSN 2059-2302. 105(1). doi: 10.1111/tan.70011. Full text in Research Archive
• Maravelia, Panagiota; Yao, Haidong; Cai, Curtis; Silva, Daniela Nascimento; Fransson, Jennifer & Nilsson, Ola B [Show all 17 contributors for this article] (2025). Unlocking novel T cell-based immunotherapy for hepatocellular carcinoma through neoantigen-driven T cell receptor isolation. Gut. ISSN 0017-5749. 74, p. 1125–1136. doi: 10.1136/gutjnl-2024-334148. Full text in Research Archive Show summary

  Background Tumour-infiltrating T cells can mediate both antitumour immunity and promote tumour progression by creating an immunosuppressive environment. This dual role is especially relevant in hepatocellular carcinoma (HCC), characterised by a unique microenvironment and limited success with current immunotherapy. Objective We evaluated T cell responses in patients with advanced HCC by analysing tumours, liver flushes and liver-draining lymph nodes, to understand whether reactive T cell populations could be identified despite the immunosuppressive environment. Design T cells isolated from clinical samples were tested for reactivity against predicted neoantigens. Single-cell RNA sequencing was employed to evaluate the transcriptomic and proteomic profiles of antigen-experienced T cells. Neoantigen-reactive T cells expressing 4-1BB were isolated and characterised through T-cell receptor (TCR)-sequencing. Results Bioinformatic analysis identified 542 candidate neoantigens from seven patients. Of these, 78 neoantigens, along with 11 hotspot targets from HCC driver oncogenes, were selected for ex vivo T cell stimulation. Reactivity was confirmed in co-culture assays for 14 targets, with most reactive T cells derived from liver flushes and lymph nodes. Liver flush-derived T cells exhibited central memory and effector memory CD4+ with cytotoxic effector profiles. In contrast, tissue-resident memory CD4+ and CD8+ T cells with an exhausted profile were primarily identified in the draining lymph nodes. Conclusion These findings offer valuable insights into the functional profiles of neoantigen-reactive T cells within and surrounding the HCC microenvironment. T cells isolated from liver flushes and tumour-draining lymph nodes may serve as a promising source of reactive T cells and TCRs for further use in immunotherapy for HCC.

• Gaimari, Anna; Lucia, Anna De; Nicolini, Fabio; Mazzotti, Lucia; Maltoni, Roberta & Rughi, Giovanna [Show all 20 contributors for this article] (2024). Significant Advancements and Evolutions in Chimeric Antigen Receptor Design. International Journal of Molecular Sciences. ISSN 1661-6596. 25(22). doi: 10.3390/ijms252212201. Full text in Research Archive
• Chiavelli, Chiara; Prapa, Malvina; Rovesti, Giulia; Silingardi, Marco; Neri, Giovanni & Pugliese, Giuseppe [Show all 23 contributors for this article] (2024). Autologous anti-GD2 CAR T cells efficiently target primary human glioblastoma. NPJ precision oncology. 8(1). doi: 10.1038/s41698-024-00506-z. Full text in Research Archive
• Silva, D.N.; Chrobok, M.; Ahlén, G.; Blomberg, P.; Sällberg, M. & Pasetto, Anna (2022). ATMP development and pre-GMP environment in academia: a safety net for early cell and gene therapy development and manufacturing. Immuno-Oncology and Technology (IOTECH). 16. doi: 10.1016/j.iotech.2022.100099. Full text in Research Archive

View all works in NVA

• Gjerdingen, Thea Johanne; Meyer, Saskia; Weis-Banke, Stine Emilie; Hansen, Marie; Ma, Jing & Yu, Di [Show all 13 contributors for this article] (2026). InsighT-1: Translating an academic TCR program into a GMP-compliant cell therapy for TdT+ ALL/LBL. Full text in Research Archive
• Gjerdingen, Thea Johanne; Meyer, Saskia; Weis-Banke, Stine Emilie; Hansen, Marie; Ma, Jing & Yu, Di [Show all 13 contributors for this article] (2026). INSIGHT-1: TRANSLATING AN ACADEMIC TCR PROGRAM INTO A GMP-COMPLIANT CELL THERAPY FOR TdT+ ALL/LBL. Cytotherapy. ISSN 1465-3249. 28(5), p. 102861–102861. doi: 10.1016/j.jcyt.2026.102861. Full text in Research Archive
• Pasetto, Anna & Lu, Yong-Chen (2023). Editorial: Personalized immunotherapy for cancer. Frontiers in Oncology. 13. doi: 10.3389/fonc.2023.1171907. Full text in Research Archive

View all works in NVA