XmAb5592 has enhanced binding affinities for human FcγRs (Kd values in nM)
| . | Fv domain specificity . | Fc domain mutations . | Binding to human Fcγ Receptors (fold increase relative to IgG1) . | ||||
|---|---|---|---|---|---|---|---|
| FcγRI . | FcγRIIa 131R . | FcγRIIa 131H . | FcγRIIIa 158F . | FcγRIIIa 158V . | |||
| XmAb5592 | HM1.24* | S239D/I332E | 0.08 ± 0.05 (4×) | 141 ± 23 (11×) | 129 ± 29 (14×) | 22 ± 4 (77×) | 8 ± 1 (36×) |
| Anti-HM1.24 IgG1 | HM1.24 | none | 0.32 ± 0.06 | 1473 ± 49 | 1750 ± 976 | 1687 ± 342 | 288 ± 78 |
| Anti-HM1.24 Fc-KO | HM1.24 | G236R/L328R | NB | NB | NB | NB | NB |
| XmAb Isotype control | RSV | S239D/I332E | 0.08 ± 0.05 (4×) | 136 ± 20 (11×) | 137 ± 21 (13×) | 20 ± 3 (84×) | 7 ± 1 (41×) |
| . | Fv domain specificity . | Fc domain mutations . | Binding to human Fcγ Receptors (fold increase relative to IgG1) . | ||||
|---|---|---|---|---|---|---|---|
| FcγRI . | FcγRIIa 131R . | FcγRIIa 131H . | FcγRIIIa 158F . | FcγRIIIa 158V . | |||
| XmAb5592 | HM1.24* | S239D/I332E | 0.08 ± 0.05 (4×) | 141 ± 23 (11×) | 129 ± 29 (14×) | 22 ± 4 (77×) | 8 ± 1 (36×) |
| Anti-HM1.24 IgG1 | HM1.24 | none | 0.32 ± 0.06 | 1473 ± 49 | 1750 ± 976 | 1687 ± 342 | 288 ± 78 |
| Anti-HM1.24 Fc-KO | HM1.24 | G236R/L328R | NB | NB | NB | NB | NB |
| XmAb Isotype control | RSV | S239D/I332E | 0.08 ± 0.05 (4×) | 136 ± 20 (11×) | 137 ± 21 (13×) | 20 ± 3 (84×) | 7 ± 1 (41×) |
Equilibrium dissociation constants (Kd) were determined from Biacore data using Langmuir fitting. Results are from at least 2 separate experiments and are mean ± SD.
NB indicates no detectable binding.
Binding affinity of humanized Fv domain used in these antibodies to HM1.24 ectodomain is 1.5 ± 0.2nM, as determined by Langmuir fitting of Biacore data. The chimeric antibody containing the original murine Fv binds HM1.24 with a Kd of 1.7 ± 0.2nM, as determined using similar methods.