MINI REVIEW article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
This article is part of the Research TopicAdvancements in Solid Tumor Immunotherapy: Enhancing Efficacy and Overcoming ResistanceView all 10 articles
Next-Generation Immunotherapy for Bladder Cancer: From the BCG Legacy to CAR-T and CAR-NK Cell Therapy "Evolving Frontiers in Bladder Cancer Immunotherapy: Integrating BCG, Immune Checkpoints, Viral Vectors, Nanotechnology, and CAR-Based Therapies"
Provisionally accepted
Anna Di Spirito1*
Gaia Zuccolotto2
Anna Tosi2
Sahar Balkhi3
Antonio Rosato2,4
Denisa Baci3
Lorenzo Mortara3*- 1Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy
- 2Istituto Oncologico Veneto IRCCS, Padua, Italy
- 3University of Insubria, Varese, Italy
- 4Department of Surgery, Oncology and Gastroenterology, University of Padova, Italy, Padova, Italy
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ABSTRACT: Bladder cancer (BC) remains a prevalent malignancy with high recurrence rates despite standard therapies. Bacille Calmette-Guérin (BCG) is the cornerstone of treatment for non-muscle-invasive bladder cancer (NMIBC); however, nearly half of patients experience relapse or develop resistance, highlighting the need for alternative strategies. Recent advances in immunotherapy have reshaped the therapeutic landscape. Immune checkpoint inhibitors (ICIs) restore T-cell function and show clinical activity in BCG-unresponsive disease. Viral vector–based approaches, including nadofaragene firadenovec and CG0070, provide localized immune activation, while cellular platforms such as CAR-T and CAR-NK therapies offer precision targeting of tumor antigens. Concurrently, nanotechnology-based delivery systems and antibody–drug conjugates (ADCs) enhance efficacy and safety by improving tumor-specific cytotoxicity. Collectively, these strategies signify a paradigm shift from traditional intravesical therapy toward personalized and durable immunotherapeutic interventions. Identification of predictive biomarkers and rational combination strategies will be critical to improving outcomes and guiding the future management of BC. Keywords: bladder cancer, immunotherapy, BCG, immune checkpoint inhibitors, viral vector therapy, CAR platforms.
Keywords: Bladder cancer, Immunotherapy, BCG, immune checkpoint inhibitors, viral vector therapy, CAR platforms
Received: 07 Oct 2025; Accepted: 21 Nov 2025.
Copyright: © 2025 Di Spirito, Zuccolotto, Tosi, Balkhi, Rosato, Baci and Mortara. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Anna Di Spirito, adispirito@uninsubria.it
Lorenzo Mortara, mortaralorenzo@gmail.com
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