Initial experience with treatment of human B cell lymphoma with anti-CD19 monoclonal antibody

Abstract

Six patients with progressive B cell non-Hodgkin's lymphoma have been treated with an IgG2a mouse monoclonal antibody (mAb) against the B cell differentiation antigen CD19, with total doses varying from 225 mg to 1000 mg. Free mAb was detected in the serum after doses of 15-30 mg. After the mAb infusions the number of circulating tumour cells was temporarily reduced, but in some cases antibody-coated cells remained in the circulation for several days. mAb penetrated to extravascular tumour sites; in general higher doses were required to saturate cells in the lymph nodes than to sensitize tumour cells in the bone marrow. mAb doses of up to 250 mg were given i.v. over 4 h without major toxicity. One patient twice achieved a partial remission after two periods of mAb treatment with an 8-month interval; the second remission lasted for 9 months. One patient showed a minor response. None of the patients made antibodies against the mouse immunoglobulin. Serum immunoglobulin levels were followed as a measure of the function of the normal B cell compartment; no significant changes were seen up to 6 months after mAb treatment.

Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy

“…Serology results from 3 subjects indicate that the remaining CD19 Several CD19-directed antibody-based immunotherapeutic approaches are currently in clinical trials for the treatment of B-cell lineage malignancies. [40][41][42] Neither preclinical nor clinical studies using such approaches have addressed the fate of PC or preexisting antigen-specific antibodies. 7,40,43 The recent introduction of CD19-directed CAR T-cell-based therapy has provided a unique opportunity to study the impact of prolonged B-cell aplasia on the CD19 2 PC population.…”

“…[40][41][42] Neither preclinical nor clinical studies using such approaches have addressed the fate of PC or preexisting antigen-specific antibodies. 7,40,43 The recent introduction of CD19-directed CAR T-cell-based therapy has provided a unique opportunity to study the impact of prolonged B-cell aplasia on the CD19 2 PC population. The duration of continuous B-cell aplasia in the cohort presented here, which was observed for at least 1827 days in 1 subject, depends on the duration of CAR T-cell persistence.…”

Superior Antitumor Activity of SAR3419 to Rituximab in Xenograft Models for Non-Hodgkin's Lymphoma

“…Binding of naked anti-CD19 to its target does not necessarily lead to cell death or antitumor activity. In one study where mouse antihuman CD19 antibody was used to treat six patients with B-cell lymphoma, antibody-coated cells remained in the circulation of some patients for several days (30). The CD19 pathway can involve Src family kinases, lead to amplification of B7-1 and B7-2 costimulatory molecules, and activate T cells (31).…”

PotentIn vitroandIn vivoActivity of an Fc-Engineered Anti-CD19 Monoclonal Antibody against Lymphoma and Leukemia

“…These have included unmodified anti-CD19 antibodies (8,9), antibody-drug conjugates (10)(11)(12), and bispecific antibodies targeting CD19 and CD3 (13) or CD16 (14) to engage cytotoxic lymphocyte effector functions. Although early clinical studies with murine unconjugated CD19 antibodies showed safety and responses in individual patients, these responses were not durable (15). However, recent phase I trials with bispecific antibodies have yielded encouraging results (16).…”