Transient blocking of both b7. 1 (cd80) and b7. 2 (cd86) in addition to cd40–cd40l interaction fully abrogates the immune response following systemic injection of adenovirus vector

ABSTRACT Blockade of the CD40–CD40L and CD80/CD86–CD28 costimulatory pathways represents a strategy to inhibit the immune response against Ad vectors designed for gene therapy applications.

Since most previous studies have used a CTLA4-Ig fusion molecule binding to both CD80 and CD86, the respective roles of these B7 molecules remained undefined. We have studied the effect of

blocking monoclonal Abs (mAbs) directed against the costimulatory molecules CD40L, CD80 and CD86, alone or in different combinations, on the humoral and cellular immune responses against Ad.

Groups of mice were transiently treated with each combination of blocking mAbs upon systemic injection of a first Ad vector. Combinations of anti-CD80 + anti-CD86 or anti-CD40L + anti-CD86

mAbs resulted in strong inhibition of the immune response against Ad. Using either of these mAb pairs, a second vector could be administered 1 month after the first injection but with lower

efficiency than in naive animals. Thus, CD86 stands as the pivotal B7 molecule involved in the development of the immune response against Ad. However, only the blockade of both CD80 and CD86

in addition to CD40L fully inhibited the humoral and cellular responses against the Ad vector, such that readministration after 1 month was as efficient as in naive animals. At the time of

readministration, treated animals had regained their ability to mount a normal immune response to the second Ad vector, showing that tolerance was not induced. Access through your

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BEING VIEWED BY OTHERS THE ENGINEERED CD80 VARIANT FUSION THERAPEUTIC DAVOCETICEPT COMBINES CHECKPOINT ANTAGONISM WITH CONDITIONAL CD28 COSTIMULATION FOR ANTI-TUMOR IMMUNITY Article Open

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DEVELOPMENT OF A FIRST-IN-CLASS VACCINE ENCODING HER2, BRACHYURY AND CD40L FOR ANTIBODY ENHANCED TUMOR ERADICATION Article Open access 30 March 2023 REFERENCES * Yang Y, Lin Q, Ertl HCJ,

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CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS We gratefully acknowledge Peter van Kooten (Faculty of Veterinary Medicine, Utrecht, NL) for the gift of

hybridoma cell lines and for his help in producing and purifying the mAbs. We thank Majid Mehtali, Ronald Rooke for critical reading of the manuscript, Bruce Acres and Monika Lusky for

helpful discussions. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * TRANSGENE, Strasbourg, France C Ziller, F Stoeckel & H Haegel-Kronenberger * Tanox Pharma BV, Amsterdam, The

Netherlands L Boon Authors * C Ziller View author publications You can also search for this author inPubMed Google Scholar * F Stoeckel View author publications You can also search for this

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search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Ziller, C., Stoeckel, F., Boon, L. _et al._ Transient

blocking of both B7.1 (CD80) and B7.2 (CD86) in addition to CD40–CD40L interaction fully abrogates the immune response following systemic injection of adenovirus vector. _Gene Ther_ 9,

537–546 (2002). https://doi.org/10.1038/sj.gt.3301684 Download citation * Received: 03 August 2001 * Accepted: 28 January 2002 * Published: 25 April 2002 * Issue Date: 01 May 2002 * DOI:

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currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * costimulatory molecules * gene therapy * adenovirus

vector