Emerging cell therapies for gastrointestinal cancers: Advances and future perspectives
Year: 2026
Type: review
Abstract: Gastrointestinal (GI) cancers, including colorectal and pancreatic cancers, remain among the most lethal cancers worldwide. These tumors often exhibit resistance to immune checkpoint inhibitors, largely due to microsatellite stability and a profoundly immunosuppressive tumor microenvironment (TME). While chimeric antigen receptor (CAR) T cell therapy has demonstrated curative potential in hematological cancers, its translation to solid tumors has been limited by challenges such as antigen heterogeneity, physical barriers to infiltration, and TME-mediated immunosuppression. Gene-editing technologies, including CRISPR-Cas9, have catalyzed the development of next-generation cellular immunotherapies. By precisely modifying T cells, natural killer (NK) cells, and mesenchymal stem/stromal cells (MSCs), it is possible to enhance their functionality, persistence, and safety. This review highlights the clinical progress of gene-edited cell therapies and specifically explores the synergistic "one-two punch" potential of engineered MSCs as TME remodeling platforms. By acting as localized delivery vehicles for cytokines or prodrug-activating enzymes, MSCs can modulate TME, thereby facilitating the infiltration and sustained cytotoxic activity of CAR T or CAR NK cells. Finally, we address critical translational challenges and propose future directions that integrate multi-omics to identify novel therapeutic agents for cellular immunotherapy in GI oncology.
Source: Molecular Therapy Oncology
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,900
Funder: Takeda Science Foundation
OpenAlex ID: W7220901370