| First Author | Gawlick U | Year | 2004 |
| Journal | Bioconjug Chem | Volume | 15 |
| Issue | 5 | Pages | 1137-45 |
| PubMed ID | 15366970 | Mgi Jnum | J:93401 |
| Mgi Id | MGI:3056982 | Doi | 10.1021/bc049911e |
| Citation | Gawlick U, et al. (2004) A conjugate of a tumor-targeting ligand and a T cell costimulatory antibody to treat brain tumors. Bioconjug Chem 15(5):1137-45 |
| abstractText | 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 tumors of treated animals. Treatment of animals with IL-12 + anti-CD28 Fab/folate prolonged survival compared to IL-12 alone. Cytokine treatment combined with tumor-targeted costimulation may be a useful adjunct treatment. |
