King’s College spin‑out advances oral HO‑1 inhibitor after mice show tumours become chemo‑sensitive

Researchers at King’s College London describe KCL‑HO‑1i, an orally available haem oxygenase‑1 inhibitor that in mice converted immunologically “cold” tumours into “hot” ones, increasing CD8+ T‑cell infiltration and boosting responses to standard chemotherapy. The lead programme has been taken forward by spin‑out Aethox Therapeutics, which plans a first‑in‑human study, but the evidence is preclinical and experts caution that safety, toxicology and regulatory hurdles must be cleared before clinical benefit can be confirmed.

Scientists at King’s College London have described a new, orally available drug candidate that in laboratory models appears to make tumours more responsive to chemotherapy by disarming an immune‑based defence mechanism. The molecule, described as KCL‑HO‑1i, was reported to improve responses in mouse models of breast cancer when given as a tablet between chemotherapy cycles, and the researchers say the compound converts immunologically “cold” tumours into “hot” ones that attract CD8+ T‑cells. According to the original report, the work was supported by Cancer Research UK and the Medical Research Council.

The science rests on a protein, haem oxygenase‑1 (HO‑1), produced by certain tumour‑associated macrophages that sit close to blood vessels. HO‑1 has antioxidant and anti‑apoptotic functions that can protect malignant cells and blunt the immune activation chemotherapy would otherwise trigger. Review literature on HO‑1 describes multiple mechanisms by which its expression in tumour and stromal cells can suppress anti‑tumour immunity and promote resistance to therapy, a rationale the KCL team used to target the pathway.

In the preclinical studies the investigators either genetically inactivated HO‑1 or inhibited it pharmacologically and reported increased infiltration of cytotoxic CD8+ T‑cells into tumours, and improved efficacy of several standard chemotherapies. Abstracts and data accompanying the work report oral bioavailability in mice with a roughly three‑hour serum half‑life and describe durable tumour control in established murine models when KCL‑HO‑1i was combined with chemotherapy. The submitted transcriptomic dataset for the programme is publicly available, which the authors say supports reproducibility of the immune changes they observed.

The laboratory programme has moved beyond the university: Aethox Therapeutics, described as a King’s College spin‑out, identifies KCL‑HO‑1i as its lead preclinical candidate and states it is preparing a first‑in‑human Phase I study (programme ATX101) in solid tumours. The company says the goal is to develop an oral companion medicine that can be given between chemotherapy sessions to reprogram the tumour microenvironment; those corporate descriptions should be read as the company’s claims pending independent clinical data.

Investigators and funders expressed guarded optimism about the clinical potential. Tanya Hollands of Cancer Research UK said the findings illustrate how combining established treatments with new agents can make better use of existing medicines and potentially boost chemotherapy’s effectiveness. The university team similarly suggested the approach could help more patients benefit from available therapies while reducing the need for more aggressive interventions. These comments were made in the original reporting and university statements accompanying the research.

Those statements come with important caveats. Experts who have reviewed the field stress that HO‑1 is a multifunctional enzyme whose inhibition may carry safety and delivery challenges, and that many promising preclinical immunomodulators fail or require dose refinement in human trials. Earlier work from the same group used a repurposed metalloporphyrin HO‑1 inhibitor as a proof of principle and underlined the need for careful phase‑I safety studies before effectiveness in people can be established.

The KCL team has suggested human trials could begin within a relatively short timeframe, but translating a mouse‑model result into a safe, effective human medicine typically involves additional pharmacology, toxicology and regulatory steps. The company and university are seeking collaboration and investment to accelerate clinical testing, while the public deposition of transcriptomic data provides a resource for independent validation of the mechanism.

If the approach proves safe and effective in people, an orally dosed HO‑1 inhibitor would be an attractive companion strategy because it could be prescribed between chemotherapy sessions without requiring hospital infusions. For now, however, the evidence is preclinical and the next crucial milestones are formal toxicity studies, regulatory approval to start first‑in‑human trials, and early clinical data that confirm both safety and the immunological effects seen in mice.

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Source: Noah Wire Services

Noah Fact Check Pro

The draft above was created using the information available at the time the story first
emerged. We’ve since applied our fact-checking process to the final narrative, based on the criteria listed
below. The results are intended to help you assess the credibility of the piece and highlight any areas that may
warrant further investigation.

Freshness check

Score:
3

Notes:
The narrative closely mirrors a report from 18 January 2018 by King’s College London, detailing the development of KCL-HO-1i, a drug designed to enhance chemotherapy effectiveness by targeting the HO-1 enzyme. ([kcl.ac.uk](https://www.kcl.ac.uk/news/new-drug-combination-kick-starts-immune-system-to-fight-cancer-4?utm_source=openai)) The recent article appears to be a republished version of this earlier content, with minimal updates. The inclusion of recent data may justify a higher freshness score but should still be flagged. The presence of the Daily Mail as the publisher raises concerns about the reliability of the information. ([standard.co.uk](https://www.standard.co.uk/news/health/james-arnold-chemotherapy-cancer-research-uk-medical-research-council-b1242319.html?utm_source=openai)) The narrative is based on a press release, which typically warrants a high freshness score. However, the lack of new information and the recycling of older material suggest a lower freshness score. The article includes updated data but recycles older material, which may justify a higher freshness score but should still be flagged.

Quotes check

Score:
2

Notes:
The quotes in the narrative are identical to those found in the 2018 King’s College London report. ([kcl.ac.uk](https://www.kcl.ac.uk/news/new-drug-combination-kick-starts-immune-system-to-fight-cancer-4?utm_source=openai)) This suggests that the quotes have been reused without significant modification, indicating a lack of originality.

Source reliability

Score:
4

Notes:
The narrative originates from the Daily Mail, a publication known for sensationalism and occasional inaccuracies. This raises concerns about the reliability of the information presented. The King’s College London report is a reputable source, but the Daily Mail’s involvement diminishes the overall reliability.

Plausability check

Score:
5

Notes:
The claims about KCL-HO-1i enhancing chemotherapy effectiveness are plausible and align with previous research from King’s College London. ([kcl.ac.uk](https://www.kcl.ac.uk/news/new-drug-combination-kick-starts-immune-system-to-fight-cancer-4?utm_source=openai)) However, the lack of new information and the recycling of older material suggest a lower plausibility score. The narrative lacks supporting detail from other reputable outlets, which is a concern. The tone and language used are consistent with typical scientific reporting, but the sensationalist headline raises questions about the narrative’s intent.

Overall assessment

Verdict (FAIL, OPEN, PASS): FAIL

Confidence (LOW, MEDIUM, HIGH): HIGH

Summary:
The narrative is a recycled version of a 2018 report from King’s College London, with minimal updates and identical quotes. The Daily Mail’s involvement raises concerns about the reliability of the information. The lack of new information and the recycling of older material suggest a lower freshness score. The narrative lacks supporting detail from other reputable outlets, which is a concern. The tone and language used are consistent with typical scientific reporting, but the sensationalist headline raises questions about the narrative’s intent.