Phase I study of expanded natural killer cells in combination with cetuximab for recurrent/metastatic nasopharyngeal carcinoma

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2022-09, Vol.71 (9), p.2277-2286
• Main Authors: Lim, Chwee Ming, Liou, Anthony, Poon, Michelle, Koh, Liang Piu, Tan, Lip Kun, Loh, Kwok Seng, Petersson, Bengt Fredrik, Ting, Eric, Campana, Dario, Goh, Boon Cher, Shimasaki, Noriko
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal, Humanized - pharmacology; Antibody-Dependent Cell Cytotoxicity; Cancer Research; CD16 antigen; Cell culture; Cell Line, Tumor; Cetuximab - pharmacology; Cetuximab - therapeutic use; Chemotherapy; Clinical Trial Report; Cytotoxicity; Epidermal growth factor; Epidermal growth factor receptors; Humans; Immunology; Killer Cells, Natural; Medicine; Medicine & Public Health; Metastases; Metastasis; Monoclonal antibodies; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - drug therapy; Nasopharyngeal Neoplasms - drug therapy; Natural killer cells; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - metabolism; Oncology; Patients; Peripheral blood; Safety; Side effects; Targeted cancer therapy; Throat cancer; Tumors
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-022-03158-9

Background Nasopharyngeal carcinoma (NPC) cells express high levels of epidermal growth factor receptor (EGFR). Cetuximab is an anti-EGFR monoclonal antibody that promotes natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) via engagement of CD16. We studied safety and efficacy of combining cetuximab with autologous expanded NK cells in patients with recurrent and/or metastatic NPC who had failed at least two prior lines of chemotherapy. Methods Seven subjects (six patients) received cetuximab every 3 weeks (six doses maximum) in the pre-trial phase. Autologous NK cells, expanded by co-culture with irradiated K562-mb15-41BBL cells, were then infused on the day after administration of cetuximab. Primary and secondary objectives were to determine safety of this combination therapy and to assess tumor responses, respectively. Results Median NK cell expansion from peripheral blood mononucleated cells after 10 days of culture with K562-mb15-41BBL was 274-fold (range, 36–534, n  = 10), and the median expression of CD16 was 98.4% (range, 67.8–99.7%). Skin rash, the commonest side effect of cetuximab in the pre-trial phase, was not exacerbated by NK cell infusion. No intolerable side effects were observed. Stable disease was observed in four subjects and progressive disease in three subjects. Three patients who received NK cells twice had time to disease progression of 12, 13, and 19 months. Conclusion NK cells with high ADCC potential can be expanded from patients with heavily pre-treated NPC. The safety profile and encouraging clinical responses observed after combining these cells with cetuximab warrant further studies of this approach. (clinicalTrials.gov NCT02507154, 23/07/2015). Precis Engaging NK cell-mediated ADCC using cetuximab plus autologous NK cells in EGFR-positive NPC was well tolerated among heavily pre-treated recurrent NPC. Promising results were observed with 3 out of 7 subjects demonstrating durable stable disease.