Next-Generation Immunotherapies: Engineering Stem Cells into Functional Immune Effectors

Adoptive immune cell therapies, such as CAR-T and NK cell therapies, have demonstrated remarkable success in certain hematologic malignancies but face limitations in scalability, donor dependence, and restricted efficacy against solid tumors. Stem cells, including induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), and mesenchymal stromal/stem cells (MSCs), offer a renewable, genetically modifiable source for generating standardized and potent immune effectors. Recent advances in differentiation protocols, genetic engineering, and synthetic biology now allow for precise reprogramming of stem cells into tailored immune cell subsets with enhanced persistence, tumor homing capacity, and resistance to immunosuppression. This rapidly emerging field holds promise for delivering next-generation, off-the-shelf cancer immunotherapies that would address unmet clinical needs and overcome the bottlenecks of current adoptive cell and gene therapy approaches.

The goal of this Research Topic is to feature cutting-edge advances at the intersection of stem cell biology/engineering and cancer immunotherapy. The central challenge in this field is to develop scalable, programmable, and clinically safe immune effector cells from renewable stem cell sources. Recent breakthroughs in genome editing, synthetic biology, and biomaterials enable us an unprecedented manipulation of stem cell fate that can be used for generation of cytotoxic cells with enhanced persistence, trafficking, and tumor-killing capabilities. By integrating knowledge from differentiation biology, tumor immunology, and translational oncology, this collection aims to showcase approaches to achieve greater in vivo persistence, increased tumor cell killing and infiltration of solid tumors, and the capacity to counter or modify the immunosuppressive tumor microenvironment (TME). Through multidisciplinary contributions, the collection aims to provide a consolidated knowledge base for rational design and (pre)clinical development of engineered immune effectors for both solid and hematologic malignancies, thereby paving the way toward novel cancer immunotherapies.

This Research Topic invites original research, reviews, mini-reviews, perspectives, and methodology reports focused on strategies to engineer stem cells into functional immune effector cells for cancer therapy. We welcome studies on generating engineered pluripotent or adult stem cells to gain specific or hybrid immune characteristics. Contributions may explore the application of synthetic biology tools, such as chimeric antigen receptors (CARs), T cell receptor (TCR) engineering, cytokine expression, immune checkpoint modulation, expression of killer ligands (e.g. TRAIL), and chemokines and their receptors in order to enhance the specificity and potency of these cells. Submissions addressing the optimization of differentiation protocols, enhancement of functional fitness, solutions to TME-mediated suppression, and functional comparisons with peripheral blood-derived immune cells are encouraged. We also invite insights into large-scale, GMP-compliant manufacturing, safety, and regulatory pathways toward clinical translation.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: stem cells, immune effectors, cancer immunotherapy, genetic engineering, mesenchymal stromal/stem cells, iPSCs, chimeric antigen receptor, tumor homing

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.