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ASH 2021: Off-the-Shelf, Multiplexed-Engineered iPSC-Derived NK Cells Mediate Potent Multi-Antigen Targeting of B-Cell Malignancies with Reduced Cytotoxicity Against Healthy B Cells

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Introduction:

Exciting research is underway to tweak already available therapies for chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL). One such study is aimed to optimize outcomes and eliminate certain ill-effects of chimeric antigen receptor (CAR) T cell therapy that targets CD19, as well as the CD-20-specific antibody, rituximab. 

In this study presented at the American Society of Hematology Annual Meeting and Exhibition (ASH 2021),  the authors evaluated the effectiveness of triple gene-modified cells, called “iDuo” Natural Killer (NK) cells. Dr. Alexey Danilov interviews Dr. Veronika Bachanova, MD, Professor of Medicine and Director of Cell Therapies and Hematologic Malignancy Department at the University of Minnesota, to discuss the topic.

Takeaways:

  • CD20-specific antibody therapies like rituximab target CD20 receptors on cancerous B-cells but can lead to loss of CD20.
  • Within one year of treatment, up to 50% of patients treated with (CAR) T cells relapse, and many of these lose CD19. Further, current (CAR) T cell treatments kill healthy and cancerous B-cells.
  • Using complex methods, a potential therapy to treat B-cell lymphomas such as CLL/SLL has been developed to minimize loss of CD19 and CD20, improve the therapeutic duration, and preferentially target malignant B-cells over normal B-cells.
  • Normal functioning NK cells circulate and destroy tumors or virus-laden cells.
  • In this study, triple gene-modified cells called iDuo NK cells were developed to facilitate multi-antigen targeting, extend therapeutic longevity and preferentially target cancerous B-cells over normal B-cells. The hope is that they would be more effective than current (CAR) T or CD20 therapies.
  • The iDuo NK cells were tested alone or in combination with rituximab against wild leukemia cells as well as more aggressive malignant Raji lymphoma cells in vitro and in mice. They appear to be more successful and longer-lasting than current (CAR) T cell or rituximab therapy.
  • Further, iDuo NK cells were tested against labeled healthy B-cells. Of significance, the iDuo NK cells preferentially targeted the lymphoma B-cells over the normal ones.
  • Currently, the first iDuo NK cell, FT596 is in Phase 1 clinical trial (NCT04245722) is underway.

Conclusions: 

Current CLL/SLL treatments such as (CAR) T cell and CD20 antibody therapies such as rituximab have drawbacks. However, ongoing research is underway using engineered triple gene-modified cells called iDuo NK cells, which can preferentially target B cancer cells, spare normal B-cells, and provide longer-lasting effectiveness over standard (CAR) T cells or rituximab therapies. While the studies are still in Phase 1 trial, hope is on the horizon.

Closing:

Watch the interview between Dr. Alexey Danilov and Dr. Veronika Bachanova:

Please enjoy the ASH abstract here.

SMART PATIENTS GET SMART CARE™. Be sure to ask your doctor about available, newer, more promising therapies or consider entering a clinical trial.

Stay Strong. We are all in this together.

Michael Green, MD and CLL patient

For information on how anti-CD20 antibodies work, see: https://cllsociety.org/2016/03/anti-cd20-antibodies-work/ For information on CAR – T cell treatment, see:  https://cllsociety.org/2022/02/can-car-t-cell-therapy-truly-cure-cll-sll/