CYNK-101 Demonstrates Anti-Tumor Activity in HNSCC Cells

The NK cell therapy is also being evaluated in a phase 1 study for acute myeloid leukemia.

The allogeneic natural killer (NK) cell therapy CYNK-101 has shown promising anti-tumor activity for EGFR+ lung cancer and head and neck squamous cell carcinoma (HNSCC) in preclinical studies.1,2

Data from Celularity’s CYNK-101 program were presented at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), November 10-14, 2021 by first author Irene Raitman Khutorskoy, PhD, principal scientist, Celularity.

“The human epidermal growth factor receptor (EGFR) has been found to be overexpressed in 40-90% of non-small cell lung cancers, with squamous cell carcinomas making up the larger proportion, and in as many as 80% of invasive HNSCC; often translating to a worse outcome for patients,” Khutorskoy and colleagues wrote.2

Khutorskoy and colleagues assessed the antibody dependent cellular cytotoxicity of CYNK-101 in combination with cetuximab against EGFR+ NSCLC and HNSCC cell lines. They first transduced human placental CD34+ cells with a lentivirus expressing CD16VP. The cells were then expanded with cytokines to generate the CYNK-101 cells. They also used Wortmannin, a PI3K kinase inhibitor, to investigate CYNK-101's mechanism of cytotoxicity.

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The investigators observed anti-tumor activity by CYNK-101 with cetuximab in vitro. They found that CYNK-101 had greater cytotoxicity with cetuximab than with control in cultured cell lines (P <.05). Analysis with Wortmannin also revealed that CYNK-101's cytotoxicity is PI3K pathway-dependent.

“CYNK-101 cells provide a combination immunotherapy option by harnessing the anti-tumor activities of both targeted biologics and innate cytotoxicity of NK cells. Further development of CYNK-101 in combination with the therapeutic antibody for these solid tumor indications is warranted,” Khutorskoy and colleagues concluded.2

Another of Celularity's candidates, CYNK-001, is being assessed in a phase 1 clinical trial (NCT04310592) that expanded its enrollment from patients with minimal residual disease (MRD) to also include patients with relapsed/refractory acute myeloid leukemia (AML).3

The expansion was prompted by a patient conversion from MRD-positive disease to MRD negativity. The patient had NPM-1–positive, FLT3-negative AML and had received the highest dose level of 5.4 billion CYNK-001 cells. The patient did not experience a dose-limiting toxicity (DLT) and had good-risk cytogenetics.

“The demonstrated ability to deliver a total [natural killer] cell dose of 5.4 billion cells in the outpatient setting without DLT and the observation of achieving a conversion from an MRD-positive to MRD-negative state on bone marrow examination with CYNK-001 cells persisting in bone marrow and blood at 28 days after day 0 infusion, is compelling and supports our trial dose escalation and indication expansion,” Robert J. Hariri, MD, PhD, founder, chairman, and chief executive officer, Celularity, said in a statement at that time.3

For more coverage of SITC 2021, click here.

REFERENCES
1. Celularity presents preclinical data on allogeneic genetically-modified natural killer cells at the Society for Immunotherapy of Cancer 36th Annual Meeting. News release. Celularity. November 15, 2021. https://celularity.com/celularity-presents-preclinical-data-on-allogeneic-genetically-modified-natural-killer-cells-at-the-society-for-immunotherapy-of-cancer-36th-annual-meeting/
2. Raitman I, Fitzgerald J, Rousseva V, et al. Developing placental CD34+-derived natural killer cells with high affinity cleavage resistant CD16 (CYNK-101) and Cetuximab for enhanced therapy of EGFR+ non-small cell lung and head and neck cancers. Presented at: 2021 SITC Annual Meeting; November 10-14, 2021; Washington, DC. Abstract 159
3. Celularity announces expansion of human placental hematopoietic stem cell derived natural killer cells (CYNK-001) phase 1 trial in patients with acute myeloid leukemia. News release. Celularity. June 29, 2021. Accessed November 15, 2021.