Criteria for identifying FcγR-mediated trogocytosis
| Criteria are as follows: . |
|---|
| In vitro experiments with cell lines or with primary cells • In the presence of acceptor cells that express FcγR, the mAb promotes transfer of its targeted antigen from the donor cell to the acceptor cell |
| • Both the mAb, its target antigen, small portions of the plasma membrane of the donor cell, and the operant FcγR of the acceptor cell are internalized by the acceptor cell |
| • The reaction is fast, going to completion in less than 1 hour at 37°C |
| • The F(ab′)2 fragments of the mAb have little or no activity in mediating trogocytosis, and inhibitors of FcγR, such as specific mAbs or high concentrations of human IgG, inhibit the reaction |
| • In vitro culture of trogocytosed cells in the absence of mAb and acceptor cells leads to re-expression of the trogocytosed antigen |
| Clinical correlative measurements specific for CLL |
| • Infusion of the mAb first promotes rapid clearance of a substantial fraction of circulating CLL cells |
| • Within 1 to 24 hours, additional cells appear in the circulation, but they express much lower levels of the mAb-targeted antigen. |
| • Trogocytosis of the targeted antigen continues for days to weeks until the plasma concentration of the mAb falls to a very low level (eg, <1 ug/ml). At this point, the level of the targeted antigen returns to close to pre-infusion levels on circulating cells. |
| Criteria are as follows: . |
|---|
| In vitro experiments with cell lines or with primary cells • In the presence of acceptor cells that express FcγR, the mAb promotes transfer of its targeted antigen from the donor cell to the acceptor cell |
| • Both the mAb, its target antigen, small portions of the plasma membrane of the donor cell, and the operant FcγR of the acceptor cell are internalized by the acceptor cell |
| • The reaction is fast, going to completion in less than 1 hour at 37°C |
| • The F(ab′)2 fragments of the mAb have little or no activity in mediating trogocytosis, and inhibitors of FcγR, such as specific mAbs or high concentrations of human IgG, inhibit the reaction |
| • In vitro culture of trogocytosed cells in the absence of mAb and acceptor cells leads to re-expression of the trogocytosed antigen |
| Clinical correlative measurements specific for CLL |
| • Infusion of the mAb first promotes rapid clearance of a substantial fraction of circulating CLL cells |
| • Within 1 to 24 hours, additional cells appear in the circulation, but they express much lower levels of the mAb-targeted antigen. |
| • Trogocytosis of the targeted antigen continues for days to weeks until the plasma concentration of the mAb falls to a very low level (eg, <1 ug/ml). At this point, the level of the targeted antigen returns to close to pre-infusion levels on circulating cells. |