| First Author | Deng J | Year | 2014 |
| Journal | Cancer Res | Volume | 74 |
| Issue | 15 | Pages | 4133-44 |
| PubMed ID | 24938765 | Mgi Jnum | J:213719 |
| Mgi Id | MGI:5585670 | Doi | 10.1158/0008-5472.CAN-14-0708 |
| Citation | Deng J, et al. (2014) Engineered fusokine GIFT4 licenses the ability of B cells to trigger a tumoricidal T-cell response. Cancer Res 74(15):4133-44 |
| abstractText | Engineered chimeric cytokines can generate gain-of-function activity in immune cells. Here, we report potent antitumor activity for a novel fusion cytokine generated by N-terminal coupling of GM-CSF to IL4, generating a fusokine termed GIFT4. B cells treated with GIFT4 clustered GM-CSF and IL4 receptors on the cell surface and displayed a pan-STAT hyperphosphorylation associated with acquisition of a distinct phenotype and function described to date. In C57BL/6J mice, administration of GIFT4 expanded endogenous B cells and suppressed the growth of B16F0 melanoma cells. Furthermore, B16F0 melanoma cells engineered to secrete GIFT4 were rejected immunologically in a B-cell-dependent manner. This effect was abolished when GIFT4-expressing B16F0 cells were implanted in B-cell-deficient mice, confirming a B-cell-dependent antitumor effect. Human GIFT4-licensed B cells primed cytotoxic T cells and specifically killed melanoma cells in vitro and in vivo. Taken together, our results demonstrated that GIFT4 could mediate expansion of B cells with potent antigen-specific effector function. GIFT4 may offer a novel immunotherapeutic tool and define a previously unrecognized potential for B cells in melanoma immunotherapy. |
