Immuno-Oncology Resource Center

Immuno-Oncology Resource Center

July 26, 2019
2 min read

Highly activated natural killer cells safe, efficient for advanced lung cancer

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Mingjie Zhang, MD, PhD
Mingjie Zhang

More than 80% of patients with advanced lung cancer achieved stable disease after receiving investigational therapy of highly activated natural killer cells, according to data published in OncoTargets and Therapy.

In the small study, 13 patients received the therapy, none of them experienced treatment-related toxicities. 

“NK cells are the only cells that play an important role in all immune functions,” Mingjie Zhang, MD, PhD, chief scientist with HANK Bioengineering, told Cell Therapy Next. HANK Bioengineering developed the highly engineered NK cells (HANKs) and sponsored the study.

Zhang said that NK cells play a major role in both immune surveillance and immune homeostasis functions, in addition to roles in immune defense and immune regulation. “Therefore, NK cell therapy should have extensive applications, including cancer, infectious diseases, inflammatory conditions, autoimmune diseases and aging,” he said.

“However,” Zhang added, “experiences with NK cells have varied. The key problem is the quality of the NK cells.”

Zhang said his company is attempting to establish “a standard for therapeutic NK cells and produce these higher-quality NK cells for clinical applications.”

Autologous HANK cells were manufactured using a method previously published by Zhang and colleagues that included isolating a patient’s NK cells and expanding them in a 2-week process until they reached a purity level greater than 80%. The process, from apheresis to infusion into the patient, takes 13 days.

Patients ceased all other pretreatments before HANK cell therapy. Each patient received at least one course of therapy; each course included three, 30-minute infusions given daily over 3 days. 

Investigators enrolled 13 patients (8 men; median age 57.3 years) in the study between March 2016 and September 2017. Patients received a diagnosis of adenocarcinoma (n = 12) or squamous cell carcinoma (n = 1); 10 patients had stage IV disease, two patients had stage III disease, and one patient had stage II disease.

There were no reports of patient discomfort, including chills or fever, during the infusions. There were no significant changes in white blood cell counts, aspartate transaminase, alanine aminotransferase, hemoglobin or creatinine levels 14 days after HANK cell infusions (P > .05) and blood, liver and renal function remained normal for all patients.

Eleven patients (84.6%) had stable disease after 3 months of autologous HANK cell therapy, two patients had disease progression (15.4%) according to RECIST guidelines. There were no reported treatment-related toxicities.

Interferon-gamma levels were significantly higher (P > .05) in patients after treatment with HANK cells. Cytokine and tumor necrosis factor-beta levels were similar before and after treatment (P > .05).

Carcinoembryonic antigen (CEA) levels significantly decreased in patients after infusion with HANK cells (2.08 ± 4.35 pmol/L vs. 2.7 ± 5.78 pmol/L; P > .05).

“Based on this and the other related research, both autologous and allogeneic HANK cells are safe and efficient for leukemia and other cancers, but allogenic HANK cells are more efficient,” Zhang said. – by Drew Amorosi


Xie S, et al. Mol Clin Oncol. 2017;doi:10.3892/mco.2017.1230.

Zhang M, et al. BMC Immunol. 2010;doi:10.1186/1471-2172-11-3.

Disclosures: Zhang is president of research and development for HANK Bioengineering.  

For more information: Mingjie Zhang, MD, PhD, can be reached at HANK Bioengineering Co., Building

119-5F, 72 Guowei Road, Shenzhen 518004, People’s Republic of China; email: