A conjugate of a tumor-targeting ligand and a T cell costimulatory antibody to treat brain tumors

Bioconjugate Chemistry
Ute GawlickEdward J Roy

Abstract

T cell immunotherapy is a potential strategy for the treatment of brain tumors because it offers a high degree of specificity, the ability to extravasate into solid tumors, and the potential for eliciting a long-term protective immune response. Various approaches have been developed to overcome T cell immune tolerance to cancer, including the use of cytokines and bispecific antibodies. T cell stimulation with the proinflammatory cytokine IL-12 can elicit antitumor immunity. T cell activation can be increased using bispecific antibodies against activating molecules on the surface of T cells and a tumor antigen. We studied the effects of systemic IL-12 administration in combination with a conjugate of an anti-CD28 antibody and a ligand for the folate receptor. The high affinity folate receptor is expressed on endogenously arising choroid plexus tumors of SV11 mice, which are transgenic for large T antigen under the control of the SV40 promoter. SV11 mice are immunocompetent, yet immunologically tolerant to large T antigen expressed by choroid plexus tumors. MRI analysis showed that the administration of IL-12 and anti-CD28 Fab/folate significantly slowed tumor growth. Proliferating CD8(+) T cells were found in choroid plexus tumo...Continue Reading

References

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Citations

Jun 6, 2012·Expert Opinion on Drug Delivery·Lesheng TengRobert J Lee
Sep 2, 2005·Journal of Pharmaceutical Sciences·Andrew R Hilgenbrink, Philip S Low
Nov 4, 2008·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Sungwon KimKinam Park

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