Radioimmunotherapy for model B cell malignancies using 90Y-labeled anti-CD19 and anti-CD20 monoclonal antibodies

Abstract

In recent years, radioimmunotherapy (RIT) with ␤ − particle emitting radionuclides targeting the CD20 antigen on B cells in the treatment of non-Hodgkin's lymphoma has provided the most compelling human clinical data for the success of RIT. CD19, like CD20, is an antigen expressed on the surface of cells of the B lineage, and CD19 may provide an alternative target for radioimmunotherapy of B cell neoplasms. CD19 has been largely overlooked as a target for conventional 131

Efficient Elimination of B-Lineage Lymphomas by Anti-CD20–Auristatin Conjugates

“…Rituximab alone has in vivo antitumor activity if co-administered with the lymphoma cell implant and dosed at Ն10 mg/kg (6). However, treatment of established tumors with rituximab administered at 10 mg/kg showed only marginal antitumor activity (22,50). Shown herein, 3 or 6 mg/kg rituximab alone were not effective against established tumors, whereas equivalent doses of rituximab-vcMMAE showed significant antitumor activity and survival advantage for the hosts (Fig.…”

“…At 4 hours before harvest, cells were incubated with Alamar Blue, a reducible dye that provides readout of cell viability (31). Table 1 50 values ranged from 48 to 300 times more potent than Dox against these cell lines. To evaluate the potency and selectivity of various antibody-drug conjugates, cells were incubated for 2 hours, washed to remove unbound antibody-drug conjugate, replated in fresh media, and incubated as above for cell viability assessment.…”

“…Although IC 50 of the free drugs differ by ϳ200-fold (Table 2), the IC 50 for the respective antibody-drug conjugate differ by Ͼ1000-fold (Table 2), suggesting a delivery advantage of MMAE-based antibodydrug conjugates. At 7.5 vcMMAE molecules per mAb molecule, the amount of free drug delivered by antibody-drug conjugate to Ramos cells at their IC 50 (40 ng/mL rituximab-vcMMAE) is 2 nmol/L.…”

Radioimmunotherapy of non-Hodgkin lymphomas

“…Earlier in development are astatine, an ␣ emitter that has been linked to rituximab and has shown in vitro activity against NHL cells, 74 and 90 Y-labeled anti-CD19, which showed activity comparable to the anti-CD20 conjugate in a lymphoma xenograft model. 75 …”

Radioimmunotherapy for Non-Hodgkin Lymphoma : Historical Perspective and Current Status

“…20 Anti-CD19, anti-CD40 or anti-idiotype antibody based RIC has been tested in mice with variable results. 21,22 A RIC for Hodgkin lymphoma with specificity for CD30 was reported to have sufficient activity in refractory patients to merit further exploration. 23 However, the most successful and clinically advanced application of RIT involved anti-CD20 antibody-based approaches using initially 131 I and subsequently 90 Y.…”