Abstract 3191: FT516, an off-the-shelf engineered NK cell therapeutic product for universal anti-tumor targeting strategy in combination with monoclonal antibodies

2019 ◽  
Author(s):  
Ryan Bjordahl ◽  
Huang Zhu ◽  
Paul Rogers ◽  
Svetlana Gaidarova ◽  
Moyar Q. Ge ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Targeting ◽  
Nk Cell ◽  
Therapeutic Product ◽  
Targeting Strategy

scholarly journals Role and Modulation of NK Cells in Multiple Myeloma

Hemato ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 167-181
Author(s):  
Marie Thérèse Rubio ◽  
Adèle Dhuyser ◽  
Stéphanie Nguyen
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Nk Cells ◽  
Tumor Cells ◽  
Nk Cell ◽  
Ex Vivo ◽  
Killer Cell ◽  
Proteasome Inhibitors ◽  
Disease Evolution ◽  
Cell Functions

Myeloma tumor cells are particularly dependent on their microenvironment and sensitive to cellular antitumor immune response, including natural killer (NK) cells. These later are essential innate lymphocytes implicated in the control of viral infections and cancers. Their cytotoxic activity is regulated by a balance between activating and inhibitory signals resulting from the complex interaction of surface receptors and their respective ligands. Myeloma disease evolution is associated with a progressive alteration of NK cell number, phenotype and cytotoxic functions. We review here the different therapeutic approaches that could restore or enhance NK cell functions in multiple myeloma. First, conventional treatments (immunomodulatory drugs-IMids and proteasome inhibitors) can enhance NK killing of tumor cells by modulating the expression of NK receptors and their corresponding ligands on NK and myeloma cells, respectively. Because of their ability to kill by antibody-dependent cell cytotoxicity, NK cells are important effectors involved in the efficacy of anti-myeloma monoclonal antibodies targeting the tumor antigens CD38, CS1 or BCMA. These complementary mechanisms support the more recent therapeutic combination of IMids or proteasome inhibitors to monoclonal antibodies. We finally discuss the ongoing development of new NK cell-based immunotherapies, such as ex vivo expanded killer cell immunoglobulin-like receptors (KIR)-mismatched NK cells, chimeric antigen receptors (CAR)-NK cells, check point and KIR inhibitors.

scholarly journals Harnessing CD16-Mediated NK Cell Functions to Enhance Therapeutic Efficacy of Tumor-Targeting mAbs

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2500
Author(s):  
Cristina Capuano ◽  
Chiara Pighi ◽  
Simone Battella ◽  
Davide De Federicis ◽  
Ricciarda Galandrini ◽  
...  
Keyword(s):  
Nk Cells ◽  
Tumor Targeting ◽  
Nk Cell ◽  
Intrinsic Resistance ◽  
Cell Functions ◽  
Adaptive Immune ◽  
Cytokines And Chemokines ◽  
Affinity Receptor ◽  
Immunosuppressive Microenvironment

Natural killer (NK) cells hold a pivotal role in tumor-targeting monoclonal antibody (mAb)-based activity due to the expression of CD16, the low-affinity receptor for IgG. Indeed, beyond exerting cytotoxic function, activated NK cells also produce an array of cytokines and chemokines, through which they interface with and potentiate adaptive immune responses. Thus, CD16-activated NK cells can concur to mAb-dependent “vaccinal effect”, i.e., the development of antigen-specific responses, which may be highly relevant in maintaining long-term protection of treated patients. On this basis, the review will focus on strategies aimed at potentiating NK cell-mediated antitumor functions in tumor-targeting mAb-based regimens, represented by (a) mAb manipulation strategies, aimed at augmenting recruitment and efficacy of NK cells, such as Fc-engineering, and the design of bi- or trispecific NK cell engagers and (b) the possible exploitation of memory NK cells, whose distinctive characteristics (enhanced responsiveness to CD16 engagement, longevity, and intrinsic resistance to the immunosuppressive microenvironment) may maximize therapeutic mAb antitumor efficacy.

scholarly journals Tumor targeting properties of monoclonal antibodies with different affinity for target antigen CD44V6 in nude mice bearing head-and-neck cancer xenografts

2002 ◽  
Vol 99 (3) ◽  
pp. 396-402 ◽  
Author(s):  
Iris Verel ◽  
Karl-Heinz Heider ◽  
Miranda Siegmund ◽  
El�nborg Ostermann ◽  
Erik Patzelt ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Nude Mice ◽  
Tumor Targeting ◽  
Target Antigen

Magnesium alterations of graft immune cells (MAGIC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18541-e18541
Author(s):  
Ramy Sedhom ◽  
Andrew Zloza ◽  
Frederick Joseph Kohlhapp ◽  
Daniel Medina ◽  
Roger Strair
Keyword(s):  
Monoclonal Antibodies ◽  
Nk Cells ◽  
Immune Cells ◽  
Nk Cell ◽  
Jurkat Cells ◽  
Nk Activity ◽  
Functional Link ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Nkg2d Expression

e18541 Background: Magnesium plays important roles in cellular processes. Allogeneic hematopoietic stem cell transplantation provides potentially curative therapy to patients with a variety of hematologic malignancies. A common abnormality post transplant is hypomagnesaemia. Recent studies identified magnesium transporter 1 deficiency in association with XMEN syndrome. These patients exhibit low intracellular [Mg++] and low T cell and NK cell NKG2D expression. Therefore, we investigated this potential functional link between magnesium deficiency and immune function in patients post transplant. Methods: A pilot study investigated whether detectable changes in T and NK cells were associated with IV magnesium repletion post hematopoietic transplant. Blood was obtained before and after magnesium transfusions. Immunophenotypic analysis of T and NK cell NKG2D levels using commercially available monoclonal antibodies (CD3, CD16, CD56, CD4, CD8, CD314 [NKG2D]) was performed. Samples from patients demonstrating an increase in NKG2D expression were subsequently analyzed for ex vivo NK activity. Here, NK activity and cytotoxicity of Jurkat cells were assayed using standard laboratory techniques and changes > 2 fold were considered significant. A total of 7 patients were enrolled. Results: NKG2D expression on T and NK cell subsets were determined by flow cytometry using commercially available monoclonal antibodies. NK reactivity and killing of K562 were undertaken using standard cytotoxicity assays. Our findings indicate a significant response in five of the seven enrolled patients. NKG2D expression on CD8+ T cells increased by up to 31%. Conclusions: Our results suggest that magnesium infusions post allogeneic transplant are associated with augmented NKG2D expression on immune cells. Additional studies are needed to clarify the mechanisms by which therapeutic magnesium repletion restores the cytotoxicity of NK cells and T lymphocytes. Although the clinical utility of magnesium supplementation remains to be validated, our data indicate that NKG2D is regulated by magnesium post transplant and magnesium may play a key role in immune regulation.

The Interplay of Antigen Affinity, Internalization, and Pharmacokinetics on CD44-Positive Tumor Targeting of Monoclonal Antibodies

2016 ◽  
Vol 13 (6) ◽  
pp. 1894-1903 ◽  
Author(s):  
Dylan M. Glatt ◽  
Denis R. Beckford Vera ◽  
Matthew C. Parrott ◽  
J. Christopher Luft ◽  
S. Rahima Benhabbour ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Targeting
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