Peptidomic Profiling of Secreted Products from Pancreatic Islet Culture Results in a Higher Yield of Full-length Peptide Hormones than Found using Cell Lysis Procedures

2013 ◽  
Vol 12 (8) ◽  
pp. 3610-3619 ◽  
Author(s):  
Steven W. Taylor ◽  
Svetlana E. Nikoulina ◽  
Nancy L. Andon ◽  
Carolyn Lowe
Keyword(s):  
Pancreatic Islet ◽  
Cell Lysis ◽  
Peptide Hormones ◽  
Full Length ◽  
Islet Culture ◽  
Peptidomic Profiling

Long-term in vitro human pancreatic islet culture using three-dimensional microfabricated scaffolds

Biomaterials ◽  
2011 ◽  
Vol 32 (6) ◽  
pp. 1536-1542 ◽  
Author(s):  
Jamal T. Daoud ◽  
Maria S. Petropavlovskaia ◽  
Jason M. Patapas ◽  
Christian E. Degrandpré ◽  
Robert W. DiRaddo ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Three Dimensional ◽  
Human Pancreatic Islet ◽  
Islet Culture

AFM11, a CD19/CD3 bispecific tandab, to facilitate T-cell-mediated killing of CD19+ cells.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3068-3068
Author(s):  
Eugene Zhukovsky ◽  
Uwe Reusch ◽  
Carmen Burkhardt ◽  
Stefan Knackmuss ◽  
Ivica Fucek ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
T Cell Activation ◽  
Xenograft Model ◽  
Cell Lysis ◽  
Full Length ◽  
Primary Tumors

3068 Background: CD19, due to broader expression on B cell subtypes, is an attractive alternative to CD20 as a target for treatment of B cell malignancies. T cells are potent tumor-killing effectors that cannot be recruited by full length antibodies, however TandAb technology harnesses their cytotoxic nature for oncology indications. The CD3 RECRUIT TandAb AFM11 enables T cells to potently and specifically kill CD19+ tumors and possesses advantageous PK properties enabling intravenous dosing. Methods: We constructed AFM11, a human bispecific tetravalent antibody with two binding sites for both CD3 and CD19. In vitro efficacy and safety were evaluated on CD19+ cell lines and primary tumors. In vivo efficacy was evaluated in a murine NOD/scid xenograft model reconstituted with human PBMC. Results: In vitro assays demonstrate higher potency and efficacy of target cell lysis by AFM11 relative to a bispecific tandem scFv. CD8+ T cells dominate early cytotoxicity (4 hrs) while after 24 hrs both CD4+ and CD8+ T cells equally contribute to tumor lysis with EC50 of 0.5 – 5 pM; cytotoxicity is independent of cell CD19 density. AFM11 exhibits similar cytotoxicity at Effector:Target ratios from 5:1 to 1:5 and facilitates T cell serial killing of its targets. AFM11 activates T cells only in the presence of CD19+ cells. In PBMC cultures AFM11 induces CD69 and CD25 expression, T cell proliferation, and production of IFN-γ, TNF-α, IL-2, IL-6, and IL-10. Depletion of CD19+ cells from PBMC abrogates these effects, and indicates strict CD19+ target-dependent T cell activation. Thus, AFM11 should not elicit the devastating cytokine release observed when full length antibodies bind CD3. Cell lysis by AFM11 is restricted to CD19+ targets asCD19- bystanders are not lysed in co-culture assays. Up to one week co-incubation with AFM11 does not inhibit T cell cytotoxicity and thus it does not induce anergy. In vivo AFM11 exhibits a dose-dependent growth inhibition of Raji tumors; a single dose of AFM11 exhibits similar efficacy as 5 daily injections. Conclusions: AFM11 is a highly efficacious novel drug candidate for the treatment of CD19+ malignancies with an advantageous safety profile and anticipated dosing regimen.

scholarly journals Pancreatic Islet Culture and Preservation Strategies: Advances, Challenges, and Future Outlook

2010 ◽  
Vol 19 (12) ◽  
pp. 1523-1535 ◽  
Author(s):  
Jamal Daoud ◽  
Lawrence Rosenberg ◽  
Maryam Tabrizian
Keyword(s):  
Pancreatic Islet ◽  
Future Outlook ◽  
Islet Culture

IMPROVED IN VIVO PANCREATIC ISLET FUNCTION AFTER PROLONGED IN VITRO ISLET CULTURE

2001 ◽  
Vol 72 (11) ◽  
pp. 1730-1736 ◽  
Author(s):  
A. Osama Gaber ◽  
Daniel W. Fraga ◽  
Christopher S. Callicutt ◽  
Ivan C. Gerling ◽  
Omaima M. Sabek ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Islet Function ◽  
Islet Culture

Use of Perfluorodecalin for Pancreatic Islet Culture Prior to Transplantation: A Liquid-Liquid Interface Culture System—Preliminary Report

2011 ◽  
Vol 20 (2) ◽  
pp. 323-332 ◽  
Author(s):  
M. T. Juszczak ◽  
A. Elsadig ◽  
A. Kumar ◽  
M. Muzyamba ◽  
K. Pawelec ◽  
...  
Keyword(s):  
Pancreatic Islet ◽  
Culture System ◽  
Preliminary Report ◽  
Liquid Interface ◽  
Islet Culture

Silver Staining of Pancreatic Islets as Revealed by Electron Microscopy

1967 ◽  
Vol 25 ◽  
pp. 44-45
Author(s):  
Kazuaki Misugi ◽  
Nobuko Misugi ◽  
Hiroshi Yamada
Keyword(s):  
Pancreatic Islet ◽  
Silver Staining ◽  
Islet Cells ◽  
Severe Hypoglycemia ◽  
Granular Cell ◽  
Electron Microscopic Level ◽  
Staining Reaction ◽  
Electron Microscopic ◽  
Pancreatic Islet Cell ◽  
D Cell

The authors had described the fine structure of a type of pancreatic islet cell, which appeared different from typical alpha and beta cells, and tentatively considered that this third type of granular cell probably represents the D cell (Figure 1).Since silver staining has been widely used to differentiate different types of pancreatic islet cells by light microscopy, an attempt to examine this staining reaction at the electron microscopic level was made.Material and Method: Surgically removed specimens from three infants who suffered from severe hypoglycemia were used. The specimens were fixed and preserved in 20% neutral formalin. Frozen sections, 30 to 40 micron thick, were prepared and they were stained by Bielschowsky's method as modified by Suzuki (2). The stained sections were examined under a microscope and islet tissues were isolated. They were fixed in 1% osmium tetroxide in phosphate buffer for one hour and embedded in Epon 812 following dehydration through a series of alcohols and propylene oxide.

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