Phase I Study of Random Healthy Donor–Derived Allogeneic Natural Killer Cell Therapy in Patients with Malignant Lymphoma or Advanced Solid Tumors

Completely allogeneic NK cells could provide a ready source of antitumor activity. This preliminary clinical trial shows that such cells are well tolerated and have potential benefits for cancer patients by upregulating the host immune responses against cancer. Natural killer (NK) cells with mismatched killer cell immunoglobulin-like receptor–ligand pairs have shown efficacy and been proven safe in treatment of cancer patients. Ex vivo–expanded and highly activated NK cells (MG4101) had been generated under good manufacturing practice conditions, which demonstrated potent anticancer activity in vitro and in vivo in preclinical studies. The current phase I clinical trial was designed to evaluate safety and possible clinical efficacy of repetitive administrations of MG4101 derived from random unrelated healthy donors into patients with malignant lymphoma or advanced, recurrent solid tumors. The maximum dose (3 × 107 cells/kg, triple infusion) was tolerable without significant adverse events. Of 17 evaluable patients, 8 patients (47.1%) showed stable disease and 9 (52.9%) showed progressive disease. We also evaluated the capacity of MG4101 to influence host immune responses. Administration of MG4101 augmented NKG2D expression on CD8+ T cells and upregulated chemokines that recruit T cells. In contrast, administration of MG4101 reduced regulatory T cells and myeloid-derived suppressor cells and suppressed TGFβ production. In conclusion, administration of a large number of MG4101 cells was not only safe and feasible, but also exhibited efficacy in maintaining the effector arm of the host immune response. Cancer Immunol Res; 4(3); 215–24. ©2016 AACR.

• Publication year

  2016

• Venue

  Cancer immunology research

• Publication date

  2016-01-19

• Fields of study

  Medicine

• Identifiers
  DOI 10.1158/2326-6066.CIR-15-0118PMID 26787822
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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