| First Author | Lode HN | Year | 2000 |
| Journal | J Clin Invest | Volume | 105 |
| Issue | 11 | Pages | 1623-30 |
| PubMed ID | 10841521 | Mgi Jnum | J:62762 |
| Mgi Id | MGI:1859536 | Doi | 10.1172/JCI9177 |
| Citation | Lode HN, et al. (2000) Melanoma immunotherapy by targeted IL-2 depends on CD4(+) T-cell help mediated by CD40/CD40L interaction. J Clin Invest 105(11):1623-30 |
| abstractText | The induction of tumor-protective immunity against malignancies remains a major challenge in cancer immunotherapy. A novel, humanized anti-ganglioside-GD(2)-IL-2 immunocytokine (hu14.18-IL-2) induced CD8(+) T cells to eradicate established pulmonary metastases of B78-D14 murine melanoma, in a process that required help by CD4(+) T cells and was mediated by the CD40/CD40 ligand (CD40L) interaction. The anti-tumor effect was diminished in mice deficient in CD4(+) T-cells. Three lines of evidence show that CD4(+) T-cell help was mediated by CD40/CD40L interaction but not by endogenous IL-2 production. First, the hu14.18-IL-2-induced anti-tumor response is partially abrogated in C57BL/6J CD40L knockout (KO) mice in contrast to C57BL/6J IL-2 KO animals, in which the immunocytokine was completely effective. Second, partial abrogation of the anti-tumor effect is induced with anti-CD40L antibodies to the same extent as with CD4(+) T-cell depletion. Third, a complete anti-tumor response induced by hu14.18-IL-2 can be reconstituted in C57BL/6J CD40L KO mice by simultaneous stimulation with an anti-CD40 mAb. These results suggest that help provided by CD4(+) T cells via CD40/CD40L interactions in our tumor model is crucial for effective immunotherapy with an IL-2 immunocytokine. |
