2003
DOI: 10.1182/blood-2002-11-3586
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Rapid recovery from T lymphopenia by CD28 superagonist therapy

Abstract: Slow recovery of T-cell numbers and function contributes to the high incidence of life-threatening infections after cytotoxic cancer therapies. We have tested the therapeutic potential of a novel class of superagonistic CD28-specific antibodies that induce polyclonal T-cell proliferation without T-cell receptor engagement in an experimental rat model of T lymphopenia.We show that in lethally irradiated, bone marrow-reconstituted hosts, CD28 superagonist is able to dramatically accelerate repopulation by a smal… Show more

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Cited by 24 publications
(20 citation statements)
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“…Alternatively, antibody therapy may be adopted in vivo using superagonist CD28-specific antibodies, which in the murine model expanded both CD4 and CD8 T cells while maintaining a diverse T-cell receptor repertoire. 20 Alemtuzumab treatment, in combination with the emerging availability of technologies that help restore T-cell functions and numbers, may hopefully enhance the safety of CD52-targeted therapy in forthcoming clinical trials. Alternatively, lower dosages of alemtuzumab could be explored to improve the safety of alemtuzumab therapy in PTL patients.…”
Section: Discussionmentioning
confidence: 99%
“…Alternatively, antibody therapy may be adopted in vivo using superagonist CD28-specific antibodies, which in the murine model expanded both CD4 and CD8 T cells while maintaining a diverse T-cell receptor repertoire. 20 Alemtuzumab treatment, in combination with the emerging availability of technologies that help restore T-cell functions and numbers, may hopefully enhance the safety of CD52-targeted therapy in forthcoming clinical trials. Alternatively, lower dosages of alemtuzumab could be explored to improve the safety of alemtuzumab therapy in PTL patients.…”
Section: Discussionmentioning
confidence: 99%
“…[12][13][14] Importantly, the stimulatory activity of CD28SA depends on the presence of an intact TCR signaling machinery delivering weak or "tonic" signals, 15,16 which are amplified by CD28 ligated by CD28SA at the level of the SLP76/Vav1/itk signalosome. 15 In rats, CD28SA have the capacity to accelerate recovery from T-lymphopenia after irradiation and bone marrow reconstitution, 17 whereas in immunocompetent rodents, a powerful induction of regulatory T cells was observed. 18,19 The latter property has been exploited in a plethora of rat and mouse models of autoimmunity, inflammation, and transplantation, with extremely encouraging results.…”
Section: Introductionmentioning
confidence: 99%
“…6 The scFv with specificity for human CD20 was generated by overlapping PCR using the published sequence of the V H -and V L -domains of the CD20 antibody 2H7. 9 These domains were linked by a glycin-serine linker (G 4 S) 3 , flanked with a BspEI and SpeI restriction site, respectively and inserted in-frame into an expression vector for bispecific antibodies described earlier. 7 Both functional scFv fragments were then linked by an 18-amino acid linker (L) derived from the N terminus of the C H1 domain (elbow region) of human IgG.…”
Section: Construction Production and Purification Of R2820mentioning
confidence: 99%
“…1 In particular, 'superagonistic' CD28 antibodies have been described which induce potent T-cell activation without a primary TCR/CD3 stimulus. 2 It has been proposed to use such antibodies for the treatment of immunodeficiency states 3 as well as autoimmune diseases. 4 Recently however, one of these antibodies, TGN1412, induced a life-threatening cytokine release syndrome in six healthy volunteers.…”
Section: Introductionmentioning
confidence: 99%