Preprint / Version 1

Effectiveness and Comparison of CAR-NK in Multiple Myeloma


  • Samuel Huang BASIS Independent Fremont Upper School



Chimeric Antigen Receptor, Natural Killer, Lymphocytes, Multiple Myeloma


Multiple myeloma (MM) is a deadly cancer of the plasma cells, which disrupts antibody production and overall health. Commonly used treatments for MM include chemotherapy, radiation therapy, and a less used CAR-T therapy. Although these therapies are mostly effective, debilitating and severe side effects can emerge. CAR-NK therapy poses a promising treatment for patients with MM, as the CAR-NK cytokine profile allows for lower side effects compared to CAR-T and still shows strong anti-tumor action. This review evaluates the mechanism and function of CAR-NK receptors and their efficacy against multiple myeloma compared to other therapies. 


Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Innate Immunity. In Molecular Biology of the Cell. 4th edition. Garland Science.

Albinger, N., Hartmann, J., & Ullrich, E. (2021). Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany. Gene Therapy, 28(9), 513–527.

Apheresis variability control. (n.d.). Cytiva. Retrieved October 29, 2023, from

CAR T cell principles. (2018, June 28). Carl DeSelm Lab.

Carpenter, R. O., Evbuomwan, M. O., Pittaluga, S., Rose, J. J., Raffeld, M., Yang, S., Gress, R. E., Hakim, F. T., & Kochenderfer, J. N. (2013). B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 19(8), 2048–2060.

Casucci, M., & Bondanza, A. (2011). Suicide Gene Therapy to Increase the Safety of Chimeric Antigen Receptor-Redirected T Lymphocytes. Journal of Cancer, 2, 378–382.

Contributors, W. E. (n.d.). Radiation Therapy for Treating Multiple Myeloma. WebMD. Retrieved October 29, 2023, from

Dotti, G., Gottschalk, S., Savoldo, B., & Brenner, M. K. (2014). Design and Development of Therapies using Chimeric Antigen Receptor-Expressing T cells. Immunological Reviews, 257(1), 10.1111/imr.12131.

Elahi, R., Heidary, A. H., Hadiloo, K., & Esmaeilzadeh, A. (2021). Chimeric Antigen Receptor-Engineered Natural Killer (CAR NK) Cells in Cancer Treatment; Recent Advances and Future Prospects. Stem Cell Reviews and Reports, 17(6), 2081.

Gunturi, A., Berg, R. E., & Forman, J. (2004). The role of CD94/NKG2 in innate and adaptive immunity. Immunologic Research, 30(1), 29–34.

Habib, S., Tariq, S. M., & Tariq, M. (2019). Chimeric Antigen Receptor-Natural Killer Cells: The Future of Cancer Immunotherapy. The Ochsner Journal, 19(3), 186–187.

Hu, Y., Tian, Z., & Zhang, C. (2018). Chimeric antigen receptor (CAR)-transduced natural killer cells in tumor immunotherapy. Acta Pharmacologica Sinica, 39(2), Article 2.

Hudspeth, K., Silva-Santos, B., & Mavilio, D. (2013). Natural Cytotoxicity Receptors: Broader Expression Patterns and Functions in Innate and Adaptive Immune Cells. Frontiers in Immunology, 4, 69.

Khawar, M. B., & Sun, H. (2021). CAR-NK Cells: From Natural Basis to Design for Kill. Frontiers in Immunology, 12.

Leddon, S. A., Fettis, M. M., Abramo, K., Kelly, R., Oleksyn, D., & Miller, J. (2020). The CD28 Transmembrane Domain Contains an Essential Dimerization Motif. Frontiers in Immunology, 11, 1519.

Leivas, A., Rio, P., Mateos, R., Paciello, M. L., Garcia-Ortiz, A., Fernandez, L., Perez-Martinez, A., Lee, D. A., Powell, D. J., Valeri, A., & Martinez-Lopez, J. (2018). NKG2D-CAR Transduced Primary Natural Killer Cells Efficiently Target Multiple Myeloma Cells. Blood, 132, 590.

Mandelboim, O., Malik, P., Davis, D. M., Jo, C. H., Boyson, J. E., & Strominger, J. L. (1999). Human CD16 as a lysis receptor mediating direct natural killer cell cytotoxicity. Proceedings of the National Academy of Sciences, 96(10), 5640–5644.

Multiple Myeloma—Statistics. (2012, June 25). Cancer.Net.

Multiple myeloma—Symptoms and causes—Mayo Clinic. (n.d.). Retrieved October 29, 2023, from

Mxpule. (2011). English: Chimeric antigen receptor. Own work.

Naeimi Kararoudi, M., Likhite, S., Elmas, E., Yamamoto, K., Schwartz, M., Sorathia, K., De Souza Fernandes Pereira, M., Sezgin, Y., Devine, R. D., Lyberger, J. M., Behbehani, G. K., Chakravarti, N., Moriarity, B. S., Meyer, K., & Lee, D. A. (2022). Optimization and validation of CAR transduction into human primary NK cells using CRISPR and AAV. Cell Reports Methods, 2(6), 100236.

Pan, K., Farrukh, H., Chittepu, V. C. S. R., Xu, H., Pan, C., & Zhu, Z. (2022). CAR race to cancer immunotherapy: From CAR T, CAR NK to CAR macrophage therapy. Journal of Experimental & Clinical Cancer Research, 41(1), 119.

Paul, S., & Lal, G. (2017). The Molecular Mechanism of Natural Killer Cells Function and Its Importance in Cancer Immunotherapy. Frontiers in Immunology, 8, 1124.

Pegram, H. J., Andrews, D. M., Smyth, M. J., Darcy, P. K., & Kershaw, M. H. (2011). Activating and inhibitory receptors of natural killer cells. Immunology and Cell Biology, 89(2), 216–224.

Pende, D., Falco, M., Vitale, M., Cantoni, C., Vitale, C., Munari, E., Bertaina, A., Moretta, F., Del Zotto, G., Pietra, G., Mingari, M. C., Locatelli, F., & Moretta, L. (2019). Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation. Frontiers in Immunology, 10.

Pfefferle, A., Jacobs, B., Haroun-Izquierdo, A., Kveberg, L., Sohlberg, E., & Malmberg, K.-J. (2020). Deciphering Natural Killer Cell Homeostasis. Frontiers in Immunology, 11, 812.

Philadelphia, T. C. H. of. (2014, March 30). Tunneled Central Line (Tunneled Central Venous Catheter) [Text]. The Children’s Hospital of Philadelphia.

Philadelphia, T. C. H. of. (2016, January 21). T Cell Collection by Apheresis [Text]. The Children’s Hospital of Philadelphia.

Protocol for generation of 3D bone marrow surrogate microenvironments in a rotary cell culture system. (n.d.). Retrieved October 29, 2023, from

Rahim, M. M. A., Tu, M. M., Mahmoud, A. B., Wight, A., Abou-Samra, E., Lima, P. D. A., & Makrigiannis, A. P. (2014). Ly49 Receptors: Innate and Adaptive Immune Paradigms. Frontiers in Immunology, 5, 145.

Rajkumar, S. V. (2022). Multiple Myeloma: 2022 update on Diagnosis, Risk-stratification and Management. American Journal of Hematology, 97(8), 1086–1107.

Sadelain, M., Brentjens, R., & Riviere, I. (2013). The basic principles of chimeric antigen receptor (CAR) design. Cancer Discovery, 3(4), 388–398.

Sameer, A. S., & Nissar, S. (2021). Toll-Like Receptors (TLRs): Structure, Functions, Signaling, and Role of Their Polymorphisms in Colorectal Cancer Susceptibility. BioMed Research International, 2021, 1157023.

Sanseviero, E. (2019). NK Cell-Fc Receptors Advance Tumor Immunotherapy. Journal of Clinical Medicine, 8(10), 1667.

Shah, U. A., & Mailankody, S. (2020). CAR T and CAR NK cells in multiple myeloma: Expanding the targets. Best Practice & Research. Clinical Haematology, 33(1), 101141.

Thorburn, A. (2007). Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Pathway Signaling. Journal of Thoracic Oncology, 2(6), 461–465.

Types of multiple myeloma | Canadian Cancer Society. (n.d.). Retrieved October 29, 2023, from

Vivier, E., Tomasello, E., Baratin, M., Walzer, T., & Ugolini, S. (2008). Functions of natural killer cells. Nature Immunology, 9(5), Article 5.

What are NK (natural killer cell) Cell Receptors. (n.d.). CUSABIO. Retrieved October 29, 2023, from

What is CAR NK therapy? | MD Anderson Cancer Center. (n.d.). Retrieved October 29, 2023, from

What You Need to Know About Multiple Myeloma. (n.d.). Retrieved October 29, 2023, from

Zhang, A., Sun, Y., Du, J., Dong, Y., Pang, H., Ma, L., Si, S., Zhang, Z., He, M., Yue, Y., Zhang, X., Zhao, W., Pi, J., Chang, M., Wang, Q., & Zhang, Y. (2021). Reducing Hinge Flexibility of CAR-T Cells Prolongs Survival In Vivo With Low Cytokines Release. Frontiers in Immunology, 12, 724211.

Zhang, L., Meng, Y., Feng, X., & Han, Z. (2022). CAR-NK cells for cancer immunotherapy: From bench to bedside. Biomarker Research, 10(1), 12.