Natural Killer Cells: A Potential New Frontier in the Fight Against Cancer?

Despite advancements in oncology research, cancer continues to be the second leading cause of death globally, according to the World Health Organization.¹ One challenge that remains is that as we learn more about cancer, we must continue to research new modalities, novel combinations, and better approaches to care to address the complexities of cancer. It means, as an industry, we need to challenge ourselves on what innovation in cancer really means so we can deliver the best to those who need it.

One novel approach we are researching in the next frontier as part of our quest to conquer cancer is natural killer (NK) cell engagers. NK-cells are a specialized immune effector cell type that play a critical role in immune activation against cancerous cells. Different from events required for T-cell activation, NK-cell activation is guided by the interaction of NK receptors with target cells, independent of antigen processing and presentation. Due to relatively simple cues for activation, NK-cells have gained significant attention in the field of cancer immunotherapy. Early safety studies of NK-cell infusion have demonstrated the potential of NK-cell infusion, even in the allogenic setting.² This bears the potential of being the next revolution in cancer treatment.

Due to relatively simple cues for activation, NK-cells have gained significant attention in the field of cancer immunotherapy. Image Credit: Adobe Stock - Alpha Tauri 3D

However, there are many challenges to overcome with NK-cell therapies, such as difficulty to meet clinical-grade ex vivo expansion, limited in vivo persistence, limited infiltration to solid tumors, and tumor editing to evade NK cell activity. As a result, various strategies are being employed to overcome these issues with the goal of improving the efficacy of NK cell-based therapy, such as ex vivo pre-conditioning with cytokines and/or small molecular drugs, developing an “off-the-shelf” NK-cell or induced pluripotent stem cell (iPSC)-differentiated chimeric antigen receptor (CAR)-NK.²

At the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, results of a first-in-human study of our investigational anti-CD123 NK-cell engager (NKCE) were shared for the first time. Our investigational trifunctional anti-CD123 NKp46×CD16 NKCE is designed to bind simultaneously to the tumor antigen CD123 and the NK-cell activating receptors, NKp46 and CD16. This 3-way engagement brings NK-cells to the leukemic CD123 cell, inducing tumor cell death. NKCEs represent another emerging technology platform under investigation to redirect NK-cells to the tumor, however, the safety and efficacy of this agent has not been evaluated by any regulatory authority.

By investigating new approaches like NKCEs, the scientific community hopes to be able to develop the next generation of immunotherapies capable of fighting cancer. This trial is ongoing and continues to recruit patients to further evaluate the safety and efficacy of our investigational NKCE.

The incredible pace of the advancements we are seeing today are unlike any approaches we have seen before in the treatment of cancer. It was inspiring to see the latest research at ASCO 2023 and how it can offer hope for patients with cancer around the world.

About the Author

Olivier Nataf is the Global Head of Oncology at Sanofi. Olivier joined Sanofi in May 2023 and has more than 20 years of industry experience leading Global strategy across therapeutic areas in France and the U.S., as well as emerging markets. In his current role as Global Head of Oncology at Sanofi, Olivier is responsible for creating and implementing the integrated vision for Sanofi’s oncology franchise.

References

1. World Health Organization. Cancer. Accessed June 2023. https://www.who.int/health-topics/cancer#tab=tab_1
2. Liu S, Galat V, Galat Y, et al. NK cell-based cancer immunotherapy: from basic biology to clinical development. J Hematol Oncol. 2021;14(7). doi:10.1186/s13045-020-01014-w