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Immunotherapy and Immune Responses / CAR-T Cell Therapy Research / Virus-based Gene Therapy Research · Journal article
Journal of Gastroenterology · September 7, 2026
Early or partial results. Treat as a signal, not a conclusion.
This is a preclinical and humanized mouse model study characterizing a novel engineered oncolytic adenovirus (ADV-PRK) that inhibits AKT signalling to trigger calreticulin-mediated dendritic cell licensing and CD8+ T cell priming. The work delineates a mechanistic pathway and demonstrates in vivo synergy with checkpoint inhibition and CAR-T therapy in murine colorectal cancer models, but provides no human efficacy data and is not designed to establish clinical benefit.
Preclinical and humanized mouse model study. Syngeneic murine colorectal cancer models and humanized mouse models; no human subjects enrolled.. Intervention: ADV-PRK: oncolytic adenovirus engineered to co-express AKT-inhibitory peptide PRK; tested as monotherapy and combined with anti-PD-1 or CAR-T cells.. Compared with: Not explicitly stated; control appears to be standard oncolytic adenovirus without PRK, but comparison is not detailed in the abstract..
ADV-PRK abrogates phosphorylation of AKT and its downstream effector IP3R3, driving ER calcium efflux and calreticulin translocation to cell surface. Surface-exposed calreticulin acts as a potent 'eat-me' signal that licenses dendritic cells to prime tumor-specific CD8+ T cells, which are essential for efficacy. ADV-PRK monotherapy achieved superior tumor control in syngeneic models (MC38, CT26).
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
This mechanism-based approach suggests a strategy to convert immunologically 'cold' tumors into environments receptive to immunotherapy. However, the work remains preclinical; clinical translation and human efficacy trials are required before any change to clinical practice can be recommended.
Mechanistic study in syngeneic and humanized mouse models demonstrating a novel immunological pathway; lacks efficacy data from human trials and is not powered to establish clinical benefit.
As stated by the source record.
This mechanism-based approach suggests a strategy to convert immunologically 'cold' tumors into environments receptive to immunotherapy. However, the work remains preclinical; clinical translation and human efficacy trials are required before any change to clinical practice can be recommended.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
What is missing. This record has no reported figures. That is a gap in the analysis, not a judgement about the study.
Abstract Background The therapeutic potential of oncolytic adenoviruses (ADVs) in colorectal cancer is constrained by a counterproductive host response: virus-triggered hyperactivation of the pro-survival AKT pathway, which fosters an immunosuppressive tumor microenvironment. Methods We engineered a novel oncolytic adenovirus, ADV-PRK, designed to co-express the AKT-inhibitory peptide PRK. Its antitumor efficacy and mechanisms were evaluated in syngeneic (MC38, CT26) and humanized mouse models. Molecular analyses (Western blot, immunofluorescence, and qPCR) elucidated signaling pathways. Immunological outcomes were assessed via flow cytometry and in vitro co-culture assays. Combination therapies with anti-PD-1 or CAR-T cells were tested in vivo. Results We demonstrate that ADV-PRK abrogates phosphorylation of both AKT and its downstream effector, the ER calcium channel IP3R3. This suppression drives ER calcium efflux, inducing calreticulin (CRT) translocation to the cell surface. Surface-exposed CRT acts as a potent “eat-me” signal, licensing dendritic cells to prime and activate tumor-specific CD8⁺ T cells, which are essential for efficacy. In vivo, ADV-PRK monotherapy achieved superior tumor control. It demonstrated potent synergy with both anti-PD-1 and CAR-T cell therapy, by remodeling the immune landscape to expand activatable T cells and support adoptive cellular therapy. Its activity in a humanized model confirms translational relevance. Conclusions Our work delineates a distinct immunomodulatory axis, AKT–IP3R3–Ca 2 ⁺–CRT, to reverse adenovirus-induced immunosuppression. This provides a translatable, mechanism-based strategy to convert immunologically “cold” tumors into environments receptive to immunotherapy, thereby offering a rational combinatorial approach to overcome resistance and significantly broaden the applicability of current immunotherapies. Graphical abstract An oncolytic adenovirus delivering the AKT-inhibitory peptide (ADV-PRK) triggers an immunogenic cascade via the AKT–IP3R3–calcium–calreticulin axis. By inducing calreticulin exposure, it arms dendritic cells to prime tumor-specific CD8⁺ T cells, ultimately synergizing with anti-PD-1 or CAR-T therapy against colorectal cancer.
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