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Cell & Gene Therapy Insights

Cell & Gene Therapy Insights

CAR-T therapy for solid tumors: early clinical trials show positive response

Studies presented at the American Association for Cancer Research (AACR) conference provide early evidence for the efficacy of CAR-T cell therapy in treating solid tumors.

CAR-T therapies have emerged as potent tools for hematologic malignancies. However, the full potential of CAR-T cell therapy in solid tumors is limited because solid tumors upregulate co-inhibitory ligands that bind to inhibitory receptors on T cells and compromises its efficacy.

Researchers around the globe are working to develop ways to enhance its efficacy in solid tumors. Two studies presented at the ongoing AACR conference provide hope for the feasibility of CAR-T therapy in solid tumors.

In the first study presented by Dr Shoba Navai of Baylor College of Medicine, CAR-T therapy was shown to be effective in patients with HER2+ sarcoma, cancer of bone and soft tissues. The study was a phase 1 dose-escalation trial where HER2-CAR T cells was intravenously administered to 10 patients with recurrent/refractory HER2+ sarcoma after lymphodepletion. The treatment was reported to be safe and effective in some patients.

The investigators found that the CAR-T cells expanded in all but two patients and CAR-T cells could be detected in all patients six weeks after infusion. In one patient where the cancer had spread to bone marrow, a complete response was observed for 12 months, but it relapsed later; retreatment with CAR-T cells resulted in a complete response that has been ongoing for 7 months. Another patient where the cancer had spread to the lungs has an ongoing complete response for 32 months.

In the second study presented by Dr Prasad Adusumilli of Memorial Sloan Kettering Cancer Center, the team investigated the safety and clinical outcome of CAR-T therapy on a particularly aggressive form of lung cancer: malignant pleural disease from mesothelioma, a cancer of the protective lining of the lung, which results typically from inhaling asbestos.

The phase 1 trial was conducted in 21 patients and tested a second generation mesothelin-targeted CAR T therapy. Called as IcasM28z, these CAR-T cells had a safety suicide gene incorporated into it which could be switched on to kill CAR-T cells in case of unintended toxicity.

CAR T cells could be detected in the peripheral blood of 13 patients during the 38-week evaluation, and their presence was associated with more than 50% decrease in the levels of a mesothelin-related peptide in the blood and evidence of tumor regression on imaging study.

14 patients were given PD-1 checkpoint inhibitors in addition to CAR-T therapy as there has been preclinical evidences that show that CAR-T cells might be exhausted in large tumors and the effect could be revived by using PD-1 agents. After up to 21 cycles of treatment with an anti -PD1 agent, two patients had complete metabolic response at 60 and 32 weeks, respectively, and these responses are ongoing; five patients had partial response, while four had stable disease. The treatment did not cause any on-target, off-tumor or therapy related toxicity.

These results showed that mesothelin-targeted CAR T-cell therapy in combination with anti-PD1 agents was more effective in eradicating tumors and the team is now planning to conduct a combination therapy trial for the same.

Source: AACR: After blood cancer successes, CAR-T treatments see inroads for solid cancers; Press Release

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