Designing multivalent proteins based on natural killer cell receptors and their ligands as immunotherapy for cancer

ABSTRACT

Introduction: Natural killer (NK) cells are an important component of the innate immune system that play a key role in host immunity against cancer. NK cell recognition and activation is based on cell surface receptors recognizing specific ligands that are expressed on many types of tumor cells. Some of these receptors are capable of activating NK cell function while other receptors inhibit NK cell function. Therapeutic approaches to treat cancer have been developed based on preventing NK cell inhibition or using NK cell receptors and their ligands to activate NK cells or T cells to destroy tumor cells.

Areas covered: This article describes the various strategies for targeting NK cell receptors and NK cell receptor ligands using multivalent proteins to activate immunity against cancer.

Expert opinion: NK cell receptors work in synergy to activate NK cell effector responses. Effective anti-cancer strategies will need to not only kill tumor cells but must also lead to the destruction of the tumor microenvironment. Immunotherapy based on NK cells and their receptors has the capacity to accomplish this through triggering lymphocyte cytotoxicity and cytokine production.

KEYWORDS:

• Cancer immunotherapy
• bispecific
• BiTE
• NK cell
• NKG2D
• CD16

Article highlights

• NK cells are important components of the innate immune system that play a key role in host immunity against cancer.

• Therapeutic approaches for cancer immunotherapy have been developed based on preventing NK cell inhibition or using NK cell receptors and their ligands to activate NK cells or T cells to destroy tumor cells.

• Strategies for targeting NK cell receptors and NK cell receptor ligands using multivalent proteins to activate immunity against cancer are being developed. The use of multivalent antibodies in anti-cancer therapy brings new advantages to antibodies, such as bispecific T cell engagers (BiTEs), bispecific and trispecific killer cell engagers (BiKEs and TriKEs).

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Declaration of interest

The work was supported in part by the National Institute of Health [CA164178] and the Center for Synthetic Immunity. CL Sentman and Dartmouth College have filed for patent protection on NK receptor-based bispecific proteins. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.