Natural Killer (NK) cells are innate lymphoid cells specialized in eliminating malignant cells through direct cytotoxicity and immunoregulatory cytokine production. Their role in cancer immunotherapy has been increasingly recognized, with clinical studies demonstrating the safety and preliminary efficacy of NK cell adoptive transfer, particularly in hematologic malignancies.
Recent advancements have focused on optimizing NK cell therapy through various strategies, including the use of different NK cell sources, isolation techniques, activation approaches, and ex vivo expansion methods. These efforts aim to enhance NK cell targeting to malignant cells, increase their functional competence, facilitate their expansion in patients, and limit inhibitory signals or cells.
One of the key findings is the importance of NK cell recognition and activation mechanisms, such as the 'missing self' and 'induced/abnormal self' signaling, which are crucial for their anti-tumor activity. Clinical trials have utilized these mechanisms to improve outcomes in patients with acute myeloid leukemia (AML), showing that adoptive NK cell therapy can induce remissions without causing graft-versus-host disease (GVHD).
Moreover, the development of novel therapeutic strategies, such as bispecific and trispecific killer cell engagers (BiKEs and TriKEs), has shown promise in enhancing NK cell targeting and activation against specific tumor antigens. These approaches, along with the use of cytokines like IL-15 to support NK cell function, represent significant steps forward in the field of NK cell-based cancer immunotherapy.
In conclusion, NK cells offer a promising avenue for cancer treatment, with ongoing research focused on overcoming current limitations and enhancing their therapeutic potential. The integration of adoptive NK cell therapy with strategies to improve targeting, augment anti-tumor responses, and limit inhibition holds the key to expanding the efficacy of NK cell immunotherapy to a broader range of malignancies.
