Role of abatacept in the management of rheumatoid arthritis

Nogid, Anna; Pham, David Q.

doi:10.1016/j.clinthera.2006.11.020

Cited by 34 publications

(18 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Abatacept is a fully human soluble fusion protein made up of the extracellular domain of human cytotoxic T lymphocyte-associated antigen 4 linked to the modified Fc portion of human IgG1 and is indicated for the treatment of refractory RA and JRA (119,194 . It acts by selectively modulating the CD80/CD86-CD28 costimulatory signal required for full T-cell activation.…”

Section: Other Biologics For Rheumatologic Diseases and Inflammatory mentioning

confidence: 99%

Infectious Complications Associated with Monoclonal Antibodies and Related Small Molecules

Salvaña

Salata

2009

Clin Microbiol Rev

View full text Add to dashboard Cite

SUMMARY Biologics are increasingly becoming part of routine disease management. As more agents are developed, the challenge of keeping track of indications and side effects is growing. While biologics represent a milestone in targeted and specific therapy, they are not without drawbacks, and the judicious use of these “magic bullets” is essential if their full potential is to be realized. Infectious complications in particular are not an uncommon side effect of therapy, whether as a direct consequence of the agent or because of the underlying disease process. With this in mind, we have reviewed and summarized the risks of infection and the infectious disease-related complications for all FDA-approved monoclonal antibodies and some related small molecules, and we discuss the probable mechanisms involved in immunosuppression as well as recommendations for prophylaxis and treatment of specific disease entities.

show abstract

Section: Other Biologics For Rheumatologic Diseases and Inflammatory mentioning

confidence: 99%

Infectious Complications Associated with Monoclonal Antibodies and Related Small Molecules

Salvaña

Salata

2009

Clin Microbiol Rev

View full text Add to dashboard Cite

show abstract

“…5 CD28 is a potential target for both inhibition and stimulation of T-cell responses. Ligand blockade with recombinant CTLA4-Ig has entered the clinic, 6 and blockade of CD28 itself by mAb or mAb fragments has been successful in rodent and primate models. [7][8][9] With regard to T-cell stimulation, mAb have been developed that activate T cells without the need to ligate the TCR, making them polyclonal T-cell activators.…”

Section: Introductionmentioning

confidence: 99%

Preculture of PBMCs at high cell density increases sensitivity of T-cell responses, revealing cytokine release by CD28 superagonist TGN1412

Römer

Berr

Avota

et al. 2011

Blood

134

150

View full text Add to dashboard Cite

Human volunteers receiving TGN1412, a humanized CD28-specific monoclonal antibody, experienced a life-threatening cytokine release syndrome during a recent trial. Preclinical tests using human PBMCs had failed to announce the rapid release of TNF, IFN-␥, and other toxic cytokines in response to this CD28 "superagonist" (CD28SA). CD28SA activate T-lymphocytes by ligating CD28 without overt engagement of the TCR. They do, however, depend on "tonic" TCR signals, which they amplify. Here we show that short-term preculture of PBMCs at high, but not at low, cell density results in massive cytokine release during subsequent stimulation with soluble TGN1412. Restoration of reactivity was cell-contact dependent, involved functional maturation of both monocytes and T cells, was sensitive to blockade by HLA-specific mAb, and was associated with TCR polarization and tyrosine phosphorylation. CD4 effector memory T cells were identified as the main source of proinflammatory cytokines. Importantly, responses to other T-cell activating agents, including microbial antigens, were also enhanced if PBMCs were first allowed to interact under tissue-like conditions. We provide a protocol, which strongly improves reactivity of circulating T cells to soluble stimulants, thereby allowing for more reliable preclinical testing of both activating and inhibitory immunomodulatory drugs. (Blood. 2011;118(26):6772-6782)

show abstract

“…Animal models demonstrated its ability to delay or even prevent the onset of allograft rejection, which is comparable to basiliximab and some polyclonal antibody therapies [114][115][116]. It has been approved for treatment of rheumatoid arthritis [117,118]. Further investigations of this medication are not currently under development.…”

Section: Abataceptmentioning

confidence: 99%