A US biotech company claims to have made the game-changing leap of using CAR T-cell therapy to treat solid tumours.
Presenting ‘proof of concept’ research findings at the CAR-TCR Summit in Boston on September 5, the California-based Eureka Therapeutics said it had achieved encouraging results in six patients with liver cancer using a novel approach that targets intracellular antigens.
The company presented preliminary findings suggesting its TCR-mimicking (TCRm) antibodies can recognise and target intracellular an AFP-peptide/HLA-A2 antigen whose breakdown products are presented on the surface of hepatocellular carcinoma (HCC) cells.
In pre-clinical studies the ET140202 T-cell therapy matched the anti-tumour efficacy of other CAR-T therapies but with a dramatic reduction cytokine release syndrome (CRS) and neurotoxicity that are serious side effects associated with CAR-T therapies.
The results presented in Boston showed that when used in six patients in China with AFP-positive hepatocellular carcinoma who had previously failed multiple lines of therapy, ET140202 T-cell therapy resulted in tumour regression in three patients.
In addition, a complete response was observed in one patient with tumour regression observed in both the primary liver tumours and distal lung metastases after multiple treatment doses. In addition, the serum AFP of this patient returned to normal levels at the five-month assessment.
Among other patients with one to three months of follow-up, two patients showed partial tumour regression, two patients showed stable disease and one patient showed progressive disease.
In vivo T-cell expansion, which indicates T-cell activation, was observed in all six patients. Reduction of serum AFP was observed in four out of the six patients.
The treatment appeared to be well-tolerated with no serious drug-related adverse events reported
“Combining T-cell therapy with a TCR-mimic antibody to target intracellular antigens is a novel approach and can potentially represent a powerful way to treat solid tumours, and in particular, liver cancer, an area of significant unmet medical need, said Eureka CEO Dr Cheng Liu (PhD).
“The initial results represent an important milestone in T-cell therapy against solid tumours, and we intend to continue to study and rapidly advance ET140202 into Phase 1 clinical trials in the US.”