Chimeric antigen receptor-engineered natural killer cells: a promising cancer immunotherapy

ABSTRACT

Introduction:

Widespread success of CD19 chimeric antigen receptor (CAR) T cells for the treatment of hematological malignancies have shifted the focus from conventional cancer treatments toward adoptive immunotherapy. There are major efforts to improve CAR constructs and to identify new target antigens. Even though the Food and Drug Administration has approved commercialization of some CD19 CART cell therapies, there are still some limitations that restrict their widespread clinical use. The manufacture of autologous products for individual patients is logistically cumbersome and expensive and allogeneic T cell products may pose an appreciable risk of graft-versus-host disease (GVHD).

Areas covered:

Natural killer (NK) cells are an attractive alternative for CART-based immunotherapies. They have the innate ability to detect and eliminate malignant cells and are safer in the ‘off-the-shelf’ setting. This review discusses the current progress within the CAR NK cell field, including the challenges, and future prospects. Gene engineered NK cells was used as the search term in PubMed and Google Scholar through to December 2020.

Expert opinion:

CAR NK cell therapies hold promise as an ‘off-the-shelf’ cell therapy for cancer. It is hoped that an enhanced understanding of their immunobiology and molecular mechanisms of action will improve their in vivo potency.

KEYWORDS:

• CAR NK
• immunotherapy
• cancer
• chimeric antigen receptors
• NK cells
• genetic engineering

Article highlights:

• Engineered NK cells retain their innate tumor-specific killing capacity thereby eliciting multiple killing mechanisms.

• NK cell signaling based CAR design holds great potential for CAR NK therapy.

• Combination therapies of CAR NK with Immune checkpoint blockers or radiation or chemotherapies could enhance efficacy.

• Advances of CAR NK therapy will start a new era of ‘off the shelf’ adoptive cell therapies for cancer.

Declaration of interest

C.M.B. is co-founder and on the scientific advisory boards for Catamaran Bio and Mana Therapeutics with stock options and/or ownership, is on the Board of Directors for Caballeta Bio with stock options and has stock in Neximmune and Repertoire Immune Medicines. C.M.B. has filed patent applications on engineered NK cells. 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 apart from those disclosed.

Additional information

Funding

This paper was supported in part by grants from the National Institutes of Health (NIH) National Cancer Institute (2P01 CA148600 and 5 U01 CA239258-02) (C.M.B.) and, the Board of Visitors of the Children’s National Health System.