Car T-cell therapy shows early promise in treating gastric cancers | cancer-research

An experimental cancer therapy that infuses designer immune cells into patients has shown early promise in a clinical trial by shrinking tumors in the digestive system.

Interim results from the first phase of the clinical trial found that the tumors in nearly half – 48.6% – of the 37 patients treated so far reduced in size after the therapy.

While the findings come from an initial safety assessment of the approach, researchers running the trial in Beijing believe it demonstrates the potential for genetically altered immune cells to treat advanced gastrointestinal cancers.

So-called Car T-cell therapy takes white blood cells, or T cells, from patients and modifies them so that they can recognize and kill cancer cells. The approach has met with dramatic success as a treatment for blood cancers such as leukaemia, but solid tumors have proved more difficult to target.

Writing in NatureMedicine, researchers led by Dr Lin Shen at the Peking University Cancer Hospital and Institute describe how they made Car T cells that target tumors bearing a protein called CLDN18.2. The protein is found in many cancers, but particularly in gastrointestinal tumours.

The researchers infused Car T cells into 37 patients with advanced cancers of the stomach, digestive tract or pancreas and found that while all experienced side-effects, the therapy had an “acceptable safety profile”. The treatment seemed most effective in those with stomach cancer, with more than 57% responding to the infusions.

The scientists stress that the findings need to be verified in the complete trial, but say the interim results suggest the approach “has the potential to become an important treatment modality for patients with advanced gastric cancer”. About 6,500 people are diagnosed with stomach cancer in the UK each year, roughly half of whom are over 75.

Waseem Qasim, professor of cell and gene therapy at the Institute of Child Health and Great Ormond Street hospital, who works on Car T-cell therapies, said the preliminary results were promising.

“The report provides some strong hints that engineered Car T cells can help shrink gastric cancers, in this case by targeting a particular flag on the surface of cells. As for other advanced solid cancers, achieving complete remissions is challenging, but the experiences shows there is potential for interventions that redirect the immune system against cancer,” he said.

Prof. Charles Swanton, Cancer Research UK’s chief clinician, said: “Car T-cell therapies, which harness modified versions of our own immune cells to fight cancer, have so far had limited success in solid tumours, which make up most cancers. So it’s particularly promising to see these results, which show a high percentage of people with digestive cancers seeing the benefits of treatment last beyond six months.

“This is encouraging, as people with digestive cancers have very few treatment options. The study is still at an early stage, and larger-scale clinical trials will need to be done before Car T-cell therapies can be used routinely in this setting.”

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