Frontiers in immunology · 2026
Novel therapeutic strategies for ccRCC through integration of systemic drug combinations and oncolytic adenovirus immunotherapy.
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Feodoroff Michaela, Mogollon Isabel, Hamdan Firas, Luck Tamara J, Kumari Romika, Bottega Paolo, Sandberg Janita, Romppanen Erika, Paavolainen Lassi, Malmstedt Minna, Penttilä Patrick, Kallioniemi Olli, Mirtti Tuomas, Rannikko Antti, Grönholm Mikaela, Cerullo Vincenzo, Pietiäinen Vilja
Аннотация
INTRODUCTION: Clear cell renal cell carcinoma (ccRCC) remains a significant therapeutic challenge due to its biological heterogeneity, variable clinical behavior, and limited efficacy of single-agent systemic therapies. Combination strategies targeting multiple tumor-promoting pathways may improve therapeutic outcomes.
METHODS: We evaluated combination treatment strategies integrating targeted systemic drugs with oncolytic adenovirus therapy using representative patient-derived cancer cell (PDC) models. Anti-tumor efficacy and immune-mediated cytotoxicity were assessed to investigate treatment responses across different patient-derived models.
RESULTS: Combination treatment enhanced anti-tumor activity compared with either monotherapy alone and promoted immune-mediated cytotoxicity involving CD8+ T cells and natural killer (NK) cells. Treatment responses varied across the three PDC models, reflecting interpatient heterogeneity and suggesting potential value for biomarker-guided patient stratification.
DISCUSSION: These findings demonstrate the potential of combining targeted therapy with oncolytic virotherapy to overcome current therapeutic limitations in ccRCC. Moreover, the use of advanced three-dimensional human-relevant PDC models provides a scalable platform for evaluating combination therapies, supporting personalized treatment strategies, and facilitating the development of therapeutic approaches applicable to ccRCC and other cancer types.
METHODS: We evaluated combination treatment strategies integrating targeted systemic drugs with oncolytic adenovirus therapy using representative patient-derived cancer cell (PDC) models. Anti-tumor efficacy and immune-mediated cytotoxicity were assessed to investigate treatment responses across different patient-derived models.
RESULTS: Combination treatment enhanced anti-tumor activity compared with either monotherapy alone and promoted immune-mediated cytotoxicity involving CD8+ T cells and natural killer (NK) cells. Treatment responses varied across the three PDC models, reflecting interpatient heterogeneity and suggesting potential value for biomarker-guided patient stratification.
DISCUSSION: These findings demonstrate the potential of combining targeted therapy with oncolytic virotherapy to overcome current therapeutic limitations in ccRCC. Moreover, the use of advanced three-dimensional human-relevant PDC models provides a scalable platform for evaluating combination therapies, supporting personalized treatment strategies, and facilitating the development of therapeutic approaches applicable to ccRCC and other cancer types.