New monoclonal antibodies and their targets in B-cell non-Hodgkin lymphoma (NHL).
| Name . | Target . | Studies/comments . |
|---|---|---|
| Abbreviations: FCR, ADCC, antibody-dependent cell-mediated cytotoxicity; CLL, chronic lymphocytic leukemia; ORR, overall response rate; CR, complete response; CHOP, cyclophosphamide, adriamycin, vincristine, prednisone; G-CSF, granulocyte colony-stimulating factor | ||
| AME-133v | CD20 | Binds with an increased affinity to FcγRIIIa (CD16). 10-fold increase in cytotoxicity relative to rituximab in vitro. Phase 1/2 study ongoing for patients with relapsed/refractory follicular lymphoma |
| GA-101 | CD20 | Glycol-engineered Fc portion and a modified elbow hinge. 50-fold higher binding affinity to the FcγRIIIa resulting in a 10 to 100-fold increase in ADCC in vitro. Apoptosis-inducer. |
| rhuMAb v114 | CD20 | 30-fold greater binding to the low-affinity variant of FcγRIIIα than to rituximab. 2 to 10 times improved ADCC relative to rituximab in vitro. |
| Ofatumumab (HuMaxCD20) | CD20 | Humanized antibody that binds to a different CD20 epitope than rituximab. Phase 1/2 trials demonstrated activity in patients with follicular lymphoma and CLL. |
| IMMU-106 (hA20) | CD20 | Humanized antibody. Phase 1/2 studies showed a 53% ORR in patients with recurrent B- cell NHL, including 6 patients that achieved CR. |
| Lumiliximab | CD23 | Active in CLL when used in combination with fludarabine-based chemotherapy. Phase 3 clinical trial comparing lumiliximab plus FCR to FCR alone currently ongoing. |
| Epratuzumab | CD22 | Epratuzumab in combination with rituximab for patients with refractory/recurrent B-cell NHL was associated with a 47% ORR and 24% CR. |
| SGN-40 | CD40 | In animal models, combination of SGN-40 with CHOP was more active than either CHOP or SGN-40 alone. Phase 1 study demonstrated activity in heavily pretreated patients with aggressive NHL. |
| HCD122 | CD40 | In vitro studies have shown that HCD122 is a more potent mediator of ADCC than rituximab. Phase 1 trial ongoing. |
| Galiximab | CD80 | Active in relapsed/refractory follicular NHL either as a single agent or in combination with rituximab. Phase 3 trial comparing galiximab plus rituximab versus rituximab plus placebo ongoing. |
| Apolizumab (Hu1D10) | HLA-DR | Active when used in combination with rituximab or G-CSF in patients with relapsed/ refractory NHL. |
| CMC-544 (immunoconjugate) | CD22 | Conjugated to calicheamicin. Clinical responses in patients with relapsed/refractory follicular lymphoma and large B-cell lymphoma. |
| BL22 | CD22 | Recombinant anti-CD22 antibody combined with Pseudomonas exotoxin. Clinical responses in hairy cell leukemia and to a lesser extent in patients with CLL. Hemolyticuremic syndrome. |
| Name . | Target . | Studies/comments . |
|---|---|---|
| Abbreviations: FCR, ADCC, antibody-dependent cell-mediated cytotoxicity; CLL, chronic lymphocytic leukemia; ORR, overall response rate; CR, complete response; CHOP, cyclophosphamide, adriamycin, vincristine, prednisone; G-CSF, granulocyte colony-stimulating factor | ||
| AME-133v | CD20 | Binds with an increased affinity to FcγRIIIa (CD16). 10-fold increase in cytotoxicity relative to rituximab in vitro. Phase 1/2 study ongoing for patients with relapsed/refractory follicular lymphoma |
| GA-101 | CD20 | Glycol-engineered Fc portion and a modified elbow hinge. 50-fold higher binding affinity to the FcγRIIIa resulting in a 10 to 100-fold increase in ADCC in vitro. Apoptosis-inducer. |
| rhuMAb v114 | CD20 | 30-fold greater binding to the low-affinity variant of FcγRIIIα than to rituximab. 2 to 10 times improved ADCC relative to rituximab in vitro. |
| Ofatumumab (HuMaxCD20) | CD20 | Humanized antibody that binds to a different CD20 epitope than rituximab. Phase 1/2 trials demonstrated activity in patients with follicular lymphoma and CLL. |
| IMMU-106 (hA20) | CD20 | Humanized antibody. Phase 1/2 studies showed a 53% ORR in patients with recurrent B- cell NHL, including 6 patients that achieved CR. |
| Lumiliximab | CD23 | Active in CLL when used in combination with fludarabine-based chemotherapy. Phase 3 clinical trial comparing lumiliximab plus FCR to FCR alone currently ongoing. |
| Epratuzumab | CD22 | Epratuzumab in combination with rituximab for patients with refractory/recurrent B-cell NHL was associated with a 47% ORR and 24% CR. |
| SGN-40 | CD40 | In animal models, combination of SGN-40 with CHOP was more active than either CHOP or SGN-40 alone. Phase 1 study demonstrated activity in heavily pretreated patients with aggressive NHL. |
| HCD122 | CD40 | In vitro studies have shown that HCD122 is a more potent mediator of ADCC than rituximab. Phase 1 trial ongoing. |
| Galiximab | CD80 | Active in relapsed/refractory follicular NHL either as a single agent or in combination with rituximab. Phase 3 trial comparing galiximab plus rituximab versus rituximab plus placebo ongoing. |
| Apolizumab (Hu1D10) | HLA-DR | Active when used in combination with rituximab or G-CSF in patients with relapsed/ refractory NHL. |
| CMC-544 (immunoconjugate) | CD22 | Conjugated to calicheamicin. Clinical responses in patients with relapsed/refractory follicular lymphoma and large B-cell lymphoma. |
| BL22 | CD22 | Recombinant anti-CD22 antibody combined with Pseudomonas exotoxin. Clinical responses in hairy cell leukemia and to a lesser extent in patients with CLL. Hemolyticuremic syndrome. |