4.8 Review

From CD16a Biology to Antibody-Dependent Cell-Mediated Cytotoxicity Improvement

Related references

Note: Only part of the references are listed.
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Donor memory-like NK cells persist and induce remissions in pediatric patients with relapsed AML after transplant

Jeffrey J. Bednarski et al.

Summary: In this study, memory-like NK cells (ML NK cells) were used to treat relapsed pediatric and young adult patients with AML after HCT. The results showed that ML NK cells can persist and exhibit potent anti-leukemic activity in a compatible post-HCT immune environment. The combination of DLI and ML NK cells provides a novel immunotherapy platform for relapsed AML.

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Systemic IL-15 promotes allogeneic cell rejection in patients treated with natural killer cell adoptive therapy

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Summary: Using IL-15 for allogeneic cellular therapy may paradoxically limit therapeutic efficacy as it accelerates CD8 T-cell activation, leading to rejection of donor NK cells.

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Feeder Cells at the Interface of Natural Killer Cell Activation, Expansion and Gene Editing

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Summary: Genome engineered natural killer (NK) cell therapies show promise in cancer immunotherapy. The use of feeder cells and genome editing technologies can enhance the anti-tumor activity of NK cells, but there are still uncertainties and complexities in the interactions between these components.

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Harnessing the Potential of NK Cell-Based Immunotherapies against Multiple Myeloma

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Summary: NK cell-based therapies show promise as anticancer treatments. The review compares autologous and allogeneic NK cell treatments for MM and their combination with existing therapies. The placement of these treatments in clinical regimens is discussed based on patient immune profiles.

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New Developments in T Cell Immunometabolism and Implications for Cancer Immunotherapy

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Phase I Trial Characterizing the Pharmacokinetic Profile of N-803, a Chimeric IL-15 Superagonist, in Healthy Volunteers

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The metabolism of cells regulates their sensitivity to NK cells depending on p53 status

Sana Belkahla et al.

Summary: Leukemic cells adapt their metabolism to support their fast proliferation and can be recognized by immune cells through activating receptors. The tumor suppressor gene p53 plays a role in cell metabolism and the expression of ligands involved in immune recognition. A chemical compound called dichloroacetate (DCA) induces the expression of these ligands in tumor cells with functional p53, sensitizing them to cytotoxic lymphocytes. DCA treatment also slows down tumor growth in vivo and could potentially enhance the effectiveness of immunotherapies using CAR T cells or NK cells.

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Escaping Death: How Cancer Cells and Infected Cells Resist Cell-Mediated Cytotoxicity

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Summary: Cytotoxic lymphocytes play a critical role in immune defense, but malignant and infected cells have ways to evade cell-mediated killing. Understanding these evasion mechanisms is important for medical interventions.

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Metformin sensitizes leukemic cells to cytotoxic lymphocytes by increasing expression of intercellular adhesion molecule-1 (ICAM-1)

Nerea Allende-Vega et al.

Summary: Solid tumor cells have altered metabolism that can protect them from cytotoxic lymphocytes, but metformin can increase tumor cell sensitivity to cytotoxic lymphocytes. Research shows that metformin induces expression of NKG2DL and ICAM-1, promoting binding between lymphocytes and tumor cells, and reducing the growth of human hematological tumor cells.

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Generating natural killer cells for adoptive transfer: expanding horizons

Soumyadipta Kundu et al.

Summary: NK cells are a unique type of innate lymphoid cells with therapeutic potential in cancer immunotherapy. They can be obtained from various sources and expanded ex vivo for therapeutic use. Developing ex vivo NK cell expansion techniques can lead to higher cell doses and application of genetic engineering methods.

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Expanded NK cells from umbilical cord blood and adult peripheral blood combined with daratumumab are effective against tumor cells from multiple myeloma patients

Chantal Reina-Ortiz et al.

Summary: The study evaluated the potential of expanded NK cells from two sources combined with mAbs to target primary multiple myeloma cells. Results indicate that umbilical cord blood eNKs are highly cytotoxic against MM cells, while peripheral blood eNKs have significant cytotoxic advantage when combined with daratumumab.

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Efficacy of Margetuximab vs Trastuzumab in Patients With Pretreated ERBB2-Positive Advanced Breast Cancer A Phase 3 Randomized Clinical Trial

Hope S. Rugo et al.

Summary: The study compared the clinical efficacy of margetuximab vs trastuzumab in patients with pretreated ERBB2-positive advanced breast cancer, showing that margetuximab had a statistically significant improvement in progression-free survival compared to trastuzumab.

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Phase I study of single agent NIZ985, a recombinant heterodimeric IL-15 agonist, in adult patients with metastatic or unresectable solid tumors

Kevin Conlon et al.

Summary: The study assessed the safety, pharmacokinetics, and immune effects of NIZ985 in patients with metastatic or unresectable solid tumors, showing promising results. Changes in dosing and combination therapy with a checkpoint inhibitor, spartalizumab, are expected to maximize the potential of NIZ985 as a novel immunotherapy.

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Immunometabolism at the Nexus of Cancer Therapeutic Efficacy and Resistance

Javier Traba et al.

Summary: This article discusses the main effects of the tumor microenvironment (TME) on the metabolism and function of immune cells, and reviews emerging strategies to boost immune cell metabolism for promoting anti-tumor effects, either as monotherapies or in combination with conventional chemotherapy for optimizing cancer treatment.

FRONTIERS IN IMMUNOLOGY (2021)

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Antibody Afucosylation Augments CD16-Mediated Serial Killing and IFNγ Secretion by Human Natural Killer Cells

Alexandros Karampatzakis et al.

Summary: The afucosylation of CD20 mAb increases NK cell cytotoxicity and IFN gamma secretion, as well as leading to faster killing of target cells and increased efficiency in serial killing by NK cells, due to the loss of CD16 causing disassembly of the immune synapse.

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NKTR-255, a novel polymer-conjugated rhIL-15 with potent antitumor efficacy

Takahiro Miyazaki et al.

Summary: NKTR-255, a novel polyethylene glycol-conjugate of rhIL-15, displayed similar in vitro properties to rhIL-15 but differed from precomplexed cytokines. NKTR-255 showed enhanced PK properties with prolonged IL-15R engagement, resulting in sustained proliferation and activation of NK and CD8(+) T cells. Furthermore, NKTR-255 demonstrated superior antitumor activity in a B-cell lymphoma model compared to precomplexed cytokines.

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Short-course IL-15 given as a continuous infusion led to a massive expansion of effective NK cells: implications for combination therapy with antitumor antibodies

Sigrid P. Dubois et al.

Summary: The study demonstrated that administering IL-15 as CIV-5 significantly expanded NK cells with increased cytotoxic functions. There were no dose-limiting toxicities in the CIV-5 regimen, and a substantial increase in CD8(+) T cells was observed.

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Hassan Dana et al.

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CD16xCD33 Bispecific Killer Cell Engager (BiKE) as potential immunotherapeutic in pediatric patients with AML and biphenotypic ALL

Sarah B. Reusing et al.

Summary: The text discusses the complexity and rarity of biphenotypic acute lymphoblastic leukemia in children, characterized by CD33 expression. Despite therapies targeting CD19, relapse and resistance remain challenges. Testing the BiKE on NK cells from healthy volunteers and leukemia patients showed enhanced effector functions against CD33(+) cells, suggesting potential as a therapeutic option.

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Antibody-receptor interactions mediate antibody-dependent cellular cytotoxicity

Yue Sun et al.

Summary: Research has shown that afucosylated monoclonal antibodies have increased affinity towards the Fc.RIIIa receptor and demonstrate heightened antibody-dependent cellular cytotoxicity. However, solution-phase data has not yet confirmed this hypothesis. Additionally, recent studies suggest that the Fab region may directly interact with Fc receptors, but the biological consequences of these interactions remain unclear.

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Daniel A. Vallera et al.

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FcεRIγ-negative NK cells persist in vivo and enhance efficacy of therapeutic monoclonal antibodies in multiple myeloma

Austin B. Bigley et al.

Summary: A subset of human natural killer (NK) cells lacking expression of Fc epsilon RI-gamma (g-NK cells) was found to significantly enhance the efficacy of therapeutic mAbs against multiple myeloma (MM), highlighting their potential to overcome current limitations of NK cell therapies.

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Susanne Wingert et al.

Summary: The newly developed bispecific antibody AFM24 shows high efficacy against tumor cells expressing varying levels of EGFR, without causing significant toxicity. This antibody demonstrates potent cell killing effects both in vitro and in vivo, indicating its potential as a promising cancer therapy.
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Altered cancer metabolism in mechanisms of immunotherapy resistance

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