Infusion reactions in natural killer cell immunotherapy: a retrospective review

Mamo, Tewodros; Williams, Shelly M.; Kinney, Stephanie; Tessier, Katelyn M.; DeFor, Todd E.; Cooley, Sarah; Miller, Jeffrey S.; McKenna, David H.

doi:10.1016/j.jcyt.2021.03.006

Cited by 8 publications

(6 citation statements)

References 41 publications

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“…Without the need for antigen presentation, NK cells can be ubiquitously effective even in cancers where tumor specific antigens remain elusive. Finally, allogeneic NK cell therapy is safe with no reports of dose limiting toxicities including graft versus host disease (GVHD), even with minimal HLA matching [15][16][17].…”

Section: Endogenous Nk Cells In B-cell Nhlmentioning

confidence: 99%

The Future of Natural Killer Cell Immunotherapy for B Cell Non-Hodgkin Lymphoma (B Cell NHL)

Chu

Lamb

Cairo

et al. 2022

Curr. Treat. Options in Oncol.

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Opinion statementNatural killer (NK) cells have played a critical—if largely unrecognized or ignored—role in the treatment of B cell non-Hodgkin lymphoma (NHL) since the introduction of CD20-directed immunotherapy with rituximab as a cornerstone of therapy over 25 years ago. Engagement with NK cells leading to lysis of NHL targets through antibody-dependent cellular cytotoxicity (ADCC) is a critical component of rituximab’s mechanism of action. Despite this important role, the only aspect of B cell NHL therapy that has been adopted as standard therapy that even indirectly augments or restores NK cell function is the introduction of obinutuzumab, a CD20 antibody with enhanced ability to engage with NK cells. However, over the last 5 years, adoptive immunotherapy with effector lymphocytes of B cell NHL has experienced tremendous growth, with five different CAR T cell products now licensed by the FDA, four of which target CD19 and have approved indications for some subtype of B cell NHL—axicabtagene ciloleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, and tisagenlecleucel. These T cell-based immunotherapies essentially mimic the recognition, activation pathway, and cytotoxic machinery of a CD19 antibody engaging NK cells and lymphoma targets. Despite their efficacy, these T cell-based immunotherapies have been difficult to implement because they require 4–6 weeks of manufacture, are costly, and have significant toxicities. This renewed interest in the potential of cellular immunity—and the manufacturing, supply chain, and administration logistics that have been addressed with these new agents—have ignited a new wave of enthusiasm for NK cell-directed therapies in NHL. With high safety profiles and proven anti-lymphoma efficacy, one or more new NK cell-directed modalities are certain to be introduced into the standard toolbox of NHL therapy within the next few years, be it function-enhancing cytokine muteins, multi-domain NK cell engagers, or adoptive therapy with expanded or genetically modified NK cells.

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Section: Endogenous Nk Cells In B-cell Nhlmentioning

confidence: 99%

The Future of Natural Killer Cell Immunotherapy for B Cell Non-Hodgkin Lymphoma (B Cell NHL)

Chu

Lamb

Cairo

et al. 2022

Curr. Treat. Options in Oncol.

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“…However, most scholars only focus on heart damage caused by anti-tumor therapy ( 25 , 26 ). Cardiotoxicity during the treatment of AL patients has been extensively reported ( 27 ), including radiotherapy ( 28 , 29 ), conventional chemotherapies (e.g., anthracyclines, antimetabolites, and cyclophosphamide) ( 30 – 32 ), immune checkpoint inhibitors (programmed cell death 1, programmed death ligand 1, or CTL-associated protein 4) ( 33 , 34 ), and many targeted therapies, particularly monoclonal antibodies and tyrosine kinase inhibitors ( 35 , 36 ), CART therapy ( 37 – 39 ), natural killer cell immunotherapy ( 40 ), and hematopoietic stem cell transplantation ( 41 – 43 ). Possible mechanisms are mediated by reactive oxygen species generated in iron-dependent chemical reactions ( 44 ), mitochondrial dysfunction ( 45 ), increased calcium flux in cardiomyocytes ( 46 ), and disorders of DNA topoisomerase 2-beta metabolism ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Cardiac-Related Lesions in Newly Diagnosed Patients With Acute Leukemia: A Chinese Population-Based Real-World Study

Xiao

Shang

et al. 2022

Front. Med.

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The relationship between newly diagnosed acute leukemia (AL) and heart-related lesions remains unclear. This study aimed to investigate baseline cardiac function and risk of cardiovascular diseases (CVDs) in patients with new-onset AL, and provide data on cardiac management strategies for patients with AL. We retrospectively collected data on baseline characteristics, echocardiography, and biochemical blood indicators (e.g., myocardial enzymes) from 408 patients, 200 with newly diagnosed AL, 103 with coronary artery disease (CAD), and 105 controls from January 1, 2015 to August 31, 2019. The creatine kinase isoenzyme myocardial band, lactate dehydrogenase, highly sensitive troponin-I, and B-type natriuretic peptide levels and left ventricular internal diameter (LVID) were significantly higher in patients with newly diagnosed AL than in the control group. The degree of cardiac damage was lower in newly diagnosed AL patients than in CAD patients. The best predictor of heart damage was LVID (AUC [area under the curve] = 0.709; 95% CI [confidence interval]: 0.637–0.781; p < 0.001), and independent prognostic risk factors were age and ejection fraction (HR [hazard ratio] = 1.636; 95% CI: 1.039–2.575; p = 0.033). The ratio of leukemia blasts among patients with AL was positively correlated with cardiac damage. Our data indicated that newly diagnosed AL patients had certain myocardial damage before treatment. Clinicians need to pay attention to these manifestations, which may be related to the prognosis.

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“…Along the same lines, whereas most reviews and original research papers claim that NK cell immunotherapy is safe and well tolerated, Mamo et al retrospectively analyzed infusion reactions in 130 cancer patients from nine different clinical trials from the same institution [ 58 ]. The patients had recurrent solid cancer in some trials and relapsed/refractory hematological cancer in the remaining ones and all had received salvage chemotherapy that had failed.…”

Section: Methods For the Massive Expansion Of Nk Cells For Immunotherapymentioning

confidence: 99%

“…With an overall response rate of 27.6%, no difference in this regard could be observed between those with severe and those with minor infusion reactions. Hematological cancers responded better than solid tumors [ 58 ].…”

Section: Methods For the Massive Expansion Of Nk Cells For Immunotherapymentioning

confidence: 99%

“…An important point here is that there was no association between the infused NK cell dose and the occurrence of grade 3 side effects, leading the authors to conclude that possibly the NK cells themselves are not responsible. Indeed, they found that the content of monocytes in the infusion product was correlated with headache and with high-grade cardiovascular effects [ 58 ]. This might be an important observation, given the requirement of monocytes and their cytokines, such as IL-1 and IL-6, for the occurrence of CRS and neurotoxicity during CAR T cell therapy [ 59 ].…”

Section: Methods For the Massive Expansion Of Nk Cells For Immunotherapymentioning

confidence: 99%

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A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

Michel

Ollert

Zimmer

2022

IJMS

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Despite significant progress in recent years, the therapeutic approach of the multiple different forms of human cancer often remains a challenge. Besides the well-established cancer surgery, radiotherapy and chemotherapy, immunotherapeutic strategies gain more and more attention, and some of them have already been successfully introduced into the clinic. Among these, immunotherapy based on natural killer (NK) cells is considered as one of the most promising options. In the present review, we will expose the different possibilities NK cells offer in this context, compare data about the theoretical background and mechanism(s) of action, report some results of clinical trials and identify several very recent trends. The pharmaceutical industry is quite interested in NK cell immunotherapy, which will benefit the speed of progress in the field.

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Infusion reactions in natural killer cell immunotherapy: a retrospective review

Cited by 8 publications

References 41 publications

The Future of Natural Killer Cell Immunotherapy for B Cell Non-Hodgkin Lymphoma (B Cell NHL)

The Future of Natural Killer Cell Immunotherapy for B Cell Non-Hodgkin Lymphoma (B Cell NHL)

Cardiac-Related Lesions in Newly Diagnosed Patients With Acute Leukemia: A Chinese Population-Based Real-World Study

A Hot Topic: Cancer Immunotherapy and Natural Killer Cells

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