Engaging natural killer cells for cancer therapy via NKG2D, CD16A and other receptors

Abstract

The field of immuno-oncology has revolutionized cancer patient care and improved survival and quality of life for patients. Much of the focus in the field has been on exploiting the power of the adaptive immune response through therapeutic targeting of T cells. While these approaches have markedly advanced the field, some challenges remain, and the clinical benefit of T cell therapies does not extend to all patients or tumor indications. Alternative strategies, such as engaging the innate immune system, have become an intense area of focus in the field. In particular, the engagement of natural killer (NK) cells as potent effectors of the innate immune response has emerged as a promising modality in immunotherapy. Here, we review therapeutic approaches for selective engagement of NK cells for cancer therapy, with a particular focus on targeting the key activating receptors NK Group 2D (NKG2D) and cluster of differentiation 16A (CD16A).

A pivotal decade for bispecific antibodies?

“…Finally, given the versatility of bsAbs and the potential to mediate completely novel MOAs, the field of bsAbs is poised to see novel emerging approaches and candidates enter the clinic, hopefully providing pivotal data in the years to come, both in oncology and in non-oncology indications, including applications in infection/virology, autoimmunity, metabolism, neurology and ophthalmology. These novel concepts include different approaches as described recently, 5 including the development of: 1) effector cell engagers different from TCEs, engaging, e.g., myeloid, NK or γδ-T cells, 96–98 2) in situ assembly concepts to specifically activate bsAbs on dual target-expressing cells 99 , 100 or in the tumor microenvironment, 101 3) PROTAC-like approaches resulting in internalization and degradation of membrane proteins, 102 4) antibody-based cytokine mimetics to trigger cytokine receptors, 103 , 104 and 5) unique solutions for delivery of bsAbs beyond barriers such as the blood-brain-barrier, 105 which may have applications for the treatment of neurodegenerative and other diseases. 106 …”

Soluble NKG2DLs Are Elevated in Breast Cancer Patients and Associate with Disease Outcome

“…Others suggest the promising use of antibodies, either to reduce serum levels of soluble ligands or to prevent shedding as well [50,51]. In March 2024, the anti-MICA/B antibody CLN-619, which inhibits shedding, received FDA approval for the treatment of relapsed/refractory multiple myeloma [52]. In 2019, Paczulla et al demonstrated that acute myeloid leukemia (AML) patients whose AML cells do not express NKG2DLs have effective immune evasion mechanisms.…”

From mechanism to therapy: the journey of CD24 in cancer

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