Abstract

BackgroundBlocking the programmed death 1 pathway by immune checkpoint inhibitors induces dramatic antitumor activity in patients with malignant tumors. However, the clinical response to immune checkpoint inhibitors remains limited owing to the patients’ immunological status, such as the number of lymphocytes, programmed death ligand 1 expression, and tumor mutation burden. In this study, we successfully treated two patients with advanced esophageal cancer who responded to the combination of adoptive immune cell therapy and a low-dose immune checkpoint inhibitor, nivolumab.Case presentationTwo Asian (Japanese) patients with advanced esophageal cancer who were resistant to conventional chemoradiation therapy were referred to our hospital for immune therapy. Case 1 was a 66-year-old woman who was diagnosed as having esophageal cancer. She received concurrent chemoradiation therapy and then underwent subtotal esophagectomy, after which she became cancer free. However, she relapsed, and cancer cells were found in the lung and lymph nodes 6 months later. She enrolled in a clinical trial at our institution (clinical trial number UMIN000028756). She received adoptive immune cell therapy twice at a 2-week interval followed by low-dose nivolumab with adoptive immune cell therapy four times at 2-week intervals. A follow-up computed tomography scan showed partial response, with mass reduction of the metastatic lung and mediastinal lesions. Case 2 was a 77-year-old man. He received concurrent chemoradiation therapy with fluoropyrimidine/platinum, and gastroscopy revealed complete remission of esophageal cancer. He was disease free for 5 months, but routine computed tomography revealed multiple metastases in his lungs and lymph nodes. He visited our clinic to receive adoptive immune cell therapy and immune checkpoint inhibitor combination therapy. Radiographic evidence showed continuous improvement of lesions. There was no evidence of severe adverse events during the combination therapy.ConclusionThe combination of adoptive immune cell therapy and an immune checkpoint inhibitor might be a possible treatment strategy for advanced esophageal cancer.Trial registration UMIN000028756. Registered 14 September 2017

Highlights

  • Blocking the programmed death 1 pathway by immune checkpoint inhibitors induces dramatic antitumor activity in patients with malignant tumors

  • We describe two cases of patients treated with the combination of Adoptive immune cell therapy (ACT) and an Immune checkpoint inhibitor (ICI); one patient was treated concurrently with ACT and an ICI, and the other patient obtained a partial response by administration of ACT and a dendritic cell (DC) vaccine followed by ICI administration for recurrence

  • The standard dose of nivolumab used in cancer therapy is usually 240 mg/kg body weight, so the dose administered in this trial was one-sixth or onetwelfth of the standard dose of nivolumab, for which no sufficient clinical data have been reported for evaluating the efficacy of nivolumab for esophageal cancer

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Summary

Conclusion

The combination of adoptive immune cell therapy and an immune checkpoint inhibitor might be a possible treatment strategy for advanced esophageal cancer.

Background
Discussion and conclusion
Findings
Patients and methods
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