New Tools to Address Old Challenges in Tolerogenic Cellular Therapies

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 30 September 2026 | Viewed by 705

Special Issue Editors


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Guest Editor
Department of Cardiac and Thoracic Aortic Surgery, Medical University of Vienna, 1090 Vienna, Austria
Interests: immune regulation; allograft rejection
1. Department of Cardiac and Thoracic Aortic Surgery, Medical University of Vienna, 1090 Vienna, Austria
2. Center for Biomedical Research and Translational Surgery, Medical University of Vienna, 1090 Vienna, Austria
Interests: transplantation; transplant immunology; regulatory T cells; immunological tolerance; alloimmunity; gd T cells; immunomodulation; cardiac transplantation
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Special Issue Information

Dear Colleagues,

Tolerogenic cellular therapies are emerging as powerful strategies to reprogram the immune system across diverse clinical contexts, including transplantation, allergy, and autoimmunity. In each of these settings, the central challenge is to achieve durable tolerance without the need for chronic immunosuppression or systemic immune suppression, which are associated with significant risks such as infection, malignancy, and toxicity. Approaches incorporating regulatory T cells (Tregs), tolerogenic dendritic cells, and chimerism-inducing protocols are being developed to recalibrate immune responses toward sustained acceptance rather than rejection due to the transplanted tissues themselves, environmental allergens, or self-antigens. However, their translation into standardized, widely applicable therapies is hindered by persistent obstacles, including the stability and scalability of cell products, the durability of tolerance, and the complexity of immune monitoring across heterogeneous patient populations.

In recent years, emerging tools in cell engineering, single-cell technologies, advanced imaging, and systems immunology have begun to open up new pathways for overcoming these challenges. CRISPR-based editing, synthetic biology, and multi-omics approaches are enabling deeper mechanistic insights and more precise therapeutic designs, while computational models are providing predictive frameworks for clinical outcomes.

For this Special Issue, “New Tools to Address Old Challenges in Tolerogenic Cellular Therapies”, we welcome contributions that critically examine how emerging methodologies can overcome persistent barriers in this field. With a scope encompassing transplantation, allergy, and autoimmunity, we will place a particular emphasis on the potential of tolerogenic strategies in achieving sustained, drug-free tolerance.

Dr. Konstantinos Mengrelis
Dr. Nina Pilat
Guest Editors

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Keywords

  • tolerogenic strategies
  • immune tolerance
  • allogeneic cellular therapies
  • autoimmunity
  • allergy
  • systems immunology
  • artificial intelligence
  • biomarkers
  • immune regulation

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Published Papers (1 paper)

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Research

17 pages, 6382 KB  
Article
Intratumoral C3ar/C5ar1 Antagonists Imbedded in an In Situ Forming Implant Can Robustly Suppress Solid Tumors
by Young A Choi, Ryan Konrad, Elliot S. Pohlmann, Eric Abenojar, Agata Exner and Edward Medof
Cells 2026, 15(11), 971; https://doi.org/10.3390/cells15110971 - 25 May 2026
Viewed by 231
Abstract
Solid tumors typically expand in a “cold” immunosuppressive tumor microenvironment (TME) and resist killing by CAR T cells or conventional therapy. Herein, we show that intratumoral injection of C3a and C5a receptor 1 (C3ar/C5ar1) pharmaceutical antagonists in an in situ forming implant (ISFI) [...] Read more.
Solid tumors typically expand in a “cold” immunosuppressive tumor microenvironment (TME) and resist killing by CAR T cells or conventional therapy. Herein, we show that intratumoral injection of C3a and C5a receptor 1 (C3ar/C5ar1) pharmaceutical antagonists in an in situ forming implant (ISFI) can robustly suppress such tumors. Antagonizing autocrine C3ar/C5ar1 signaling in eight human and murine cancers of diverse lineages was universally anti-mitotic and pro-apoptotic in vitro, and growth-repressive in vivo. In contrast to i.p. administration of C3ar/C5ar1 antagonists to tumor-bearing mice, injecting the antagonists intratumorally in slow release poly (lactic-co-glycolic acid) (PLGA) polymer caused near-complete tumor elimination. The focused blockade of C3ar/C5ar1 GPCR signaling in an intratumoral ISFI opposed solid cancers by jointly repressing cancer cell viability/growth, tumor-associated angiogenesis, and myeloid-derived suppressor cell (MDSC) recruitment. Thus, the sustained blockade of C3ar/C5ar1 signaling in an intratumoral ISFI uninterruptedly disrupts three processes essential for solid cancer growth while avoiding adverse effects on other cell types. Our findings may apply to multiple cancer types in which discrete tumor masses can be targeted. Full article
(This article belongs to the Special Issue New Tools to Address Old Challenges in Tolerogenic Cellular Therapies)
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