A pilot trial of humanized anti-GD2 monoclonal antibody (hu14.18K322A) with chemotherapy and natural killer cells in children with recurrent/refractory neuroblastoma

Sara M. Federico, M. Beth McCarville, Barry L. Shulkin, Paul M. Sondel, Jacquelyn A. Hank, Paul Hutson, Michael Meagher, Aaron Shafer, Catherine Y. Ng, Wing Leung, William E. Janssen, Jianrong Wu, Shenghua Mao, Rachel C. Brennan, Victor M. Santana, Alberto S. Pappo, Wayne L. Furman

Research output: Contribution to journalArticlepeer-review

106 Scopus citations


Purpose: Anti-GD2 mAbs, acting via antibody-dependent cell-mediated cytotoxicity, may enhance the effects of chemotherapy. This pilot trial investigated a fixed dose of a unique anti-GD2 mAb, hu14.18K322A, combined with chemotherapy, cytokines, and haploidentical natural killer (NK) cells. Experimental Design: Children with recurrent/refractory neuroblastoma received up to six courses of hu14.18K322A (40 mg/m2/dose, days 2–5), GM-CSF, and IL2 with chemotherapy: cyclophosphamide/topotecan (courses 1,2), irinotecan/temozolomide (courses 3,4), and ifosfamide/carboplatin/ etoposide (courses 5,6). Parentally derived NK cells were administered with courses 2, 4, and 6. Serum for pharmacokinetic studies of hu14.18K322A, soluble IL2 receptor alpha (sIL2Ra) levels, and human antihuman antibodies (HAHA) were obtained. Results: Thirteen heavily pretreated patients (9 with prior anti-GD2 therapy) completed 65 courses. One patient developed an unacceptable toxicity (grade 4 thrombocytopenia >35 days). Four patients discontinued treatment for adverse events (hu14.18K322A allergic reaction, viral infection, surgical death, second malignancy). Common toxicities included grade 3/4 myelosuppression (13/13 patients) and grade 1/2 pain (13/13 patients). Eleven patients received 29 NK-cell infusions. The response rate was 61.5% (4 complete responses, 1 very good partial response, 3 partial responses) and five had stable disease. The median time to progression was 274 days (range, 239–568 days); 10 of 13 patients (77%) survived 1 year. Hu14.18K322A pharmacokinetics was not affected by chemotherapy or HAHA. All patients had increased sIL2Ra levels, indicating immune activation. Conclusions: Chemotherapy plus hu14.18K322A, cytokines, and NK cells is feasible and resulted in clinically meaningful responses in patients with refractory/recurrent neuroblastoma. Further studies of this approach are warranted in patients with relapsed and newly diagnosed neuroblastoma.

Original languageEnglish
Pages (from-to)6441-6449
Number of pages9
JournalClinical Cancer Research
Issue number21
StatePublished - Nov 1 2017

Bibliographical note

Funding Information:
Supported in part by Cancer Center GrantCA23099 and Cancer Center Support CORE GrantP30 CA 21765 from the National Cancer Institute and by the American Lebanese Syrian Associated Charities.

Publisher Copyright:
©2017 AACR.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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