Clinical study of PD-1 disrupted anti-MUC1 CAR-T cells in patients with advanced oesophageal cancer
- Publisher:
- Elsevier
- Publication Type:
- Conference Proceeding
- Citation:
- Annals of Oncology, 2021, 32, pp. S186-S186
- Issue Date:
- 2021-06-30
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| P-258 Clinical study of PD-1 disrupted anti-MUC1 CAR-T cells in patients with advanced oesophageal cancer - Annals of Oncology.pdf | Published version | 103.99 kB |
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Background: In this report we evaluated the safety and efficacy of PD-1 knockout engineered anti-MUC1 CART cells in the treatment of patients with advanced oesophageal cancer (NCT03706326). This study builds on our previous work, which studied the safety of these engineered CAR-T cells in patients with advanced non-small cell lung cancer (Lin et al: Ann Oncol 30. doi: 10.1093/annonc/mdz448, 2019). Both studies explored PD-1/CART treatment in solid tumour types.
Methods: Patients (age ≥ 18) were recruited according to the criteria documented in NCT03706326. MUC1-specific CARs were constructed using SM3 scFv. Following lenti-MUC1 CAR retroviral transduction, efficiency of transgenic expression was assessed by flow cytometry. PD-1 gene KO in the CAR positive T cells was achieved using the CRISPR-Cas9 system and validated by sequencing and flow cytometry. MUC1-CAR+/PD-1- KO engineered T cells at a starting dose of 2.5x106/KG were infused over 60 mins. Following treatment, patients’ general condition, levels of lymphocytes, IL-6, hs-CRP, PCT, CYFRA21, NSE(E), and SCC were monitored at regular intervals. Circulating CART cells were checked regularly. Changes in tumour size were examined by MRI scans. The primary endpoint was to assess the safety of this treatment. We also compared the responses in patients who received single and multiple cycles of infusion of therapeutic CART cells.
Results: The data was obtained from patients enrolled in the clinical trial between February 2019 - March 2021. Up to the cutoff date (February 11, 2021), 8 patients diagnosed with oesophageal cancer/oesophageal squamous cell carcinoma NSCLC (IIIb to IV), were recruited for this study. All participants received at least one cycle of anti-MUC1 CART cell treatment. Among the 8 treated patients, 5 received 1 cycle, 1 received 2 cycles, 1 received 6 cycles, and 1 received 8 cycles. The most common adverse events (AE) were acute fever (6 patients, 38.0-40.5 C◦), chills (2 patients, occurred in the subsequent cycle of infusion), skin rash (1 patient). No grade 3-5 AEs were found, and no cytokine release syndrome (CRS) was observed. Of the 8 assessed patients, 5 had stable disease (SD) while 3 had progressive disease. All patients had significant symptom improvements after infusion. Circulating CART cells gradually declined after infusion; the number dropped down to approximately 25% in 4 months after one cycle treatment indicating the necessity of receiving more cycles. The patients who received multiple cycle of infusion showed long term and steady SD status.
Conclusions: Our preliminary data suggests that the treatment of oesophageal cancer patients with PD-1 disrupted anti- MUC1-CAR cells is safe and well tolerated by all patients. No CRS was observed throughout the study. The efficacy of this unique combined therapy is currently being assessed. Our limited data indicates that the best achievable clinical outcome is SD meaning that the anticancer effect of current CART cells with PD-1 inhibition on solid tumours have a ceiling.
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