Targeted anti-cancer therapy using rituximab, a chimaeric anti-CD20 antibody (IDEC-C2B8) in the treatment of non-Hodgkin's B-cell lymphoma

Anderson, Dana R.; Grillo-López, Antonio J; Varns, C.; Chambers, Karen S.; Hanna, Nabil

doi:10.1042/bst0250705

Cited by 231 publications

(125 citation statements)

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“…The strong correlation between therapeutic performance in vivo and antibody-dependent cellular cytotoxicity in vitro helped to establish the belief that cytotoxic cellular effectors as well as complement-dependent lysis provide the main arm of C2B8 activity. 1,[9][10][11][12] In addition to these indirect cytotoxic effects, cross-linking of CD20 with C2B8 further induces growth inhibiting and apoptotic signals in lymphoma cell lines. [13][14][15][16][17][18][19] Our results presented in this study also clearly demonstrate that treatment of the Burkitt lymphoma cell Daudi with mAb C2B8 triggered pronounced apoptotic cell death within hours in the absence of immune effector cells or complement (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

“…Results from in vitro studies demonstrate that binding of mAb C2B8 to CD20 cell surface molecules on B cells induces complementdependent lysis of target cells as well as antibody-dependent cellular cytotoxicity mediated by macrophages and NK cells. 1,[9][10][11][12] Yet it is more and more believed that signalling mechanisms induced by mAb C2B8 leading to apoptosis are potentially more important, since crosslinking of surface CD20 molecules with mAb C2B8 induces growth arrest and apoptosis in B cells. [13][14][15][16][17][18][19] Correspondence Recent studies have clearly shown that dendritic cells (DC) can ingest apoptotic or necrotic cells and present peptides thereof on MHC class II but also on MHC class I molecules.…”

Section: Introductionmentioning

confidence: 99%

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CD20 antibody (C2B8)-induced apoptosis of lymphoma cells promotes phagocytosis by dendritic cells and cross-priming of CD8+ cytotoxic T cells

et al. 2001

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CD20 antibody (C2B8)-induced apoptosis of lymphoma cells promotes phagocytosis by dendritic cells and cross-priming of CD8+ cytotoxic T cells

et al. 2001

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“…Various in vitro and in vivo experiments have shown that elimination of CD20þ lymphoma cells by rituximab involves complement-dependent cytotoxicity (CDC; refs [16][17][18][19][20][21][22][23], direct induction of apoptotic signalling (24)(25)(26), as well as the recruitment of effector cells leading to antibody-dependent cell-mediated cytotoxicity (27). Nevertheless, the in vivo mechanism of action of and resistance to rituximab are not fully understood (28).…”

Section: Introductionmentioning

confidence: 99%

Preclinical Studies on the Mechanism of Action and the Anti-Lymphoma Activity of the Novel Anti-CD20 Antibody GA101

Dalle

Reslan

Horts

et al. 2011

Molecular Cancer Therapeutics

115

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GA101 is a novel glycoengineered Type II CD20 monoclonal antibody. When compared with rituximab, it mediates less complement-dependent cytotoxicity (CDC). As expected for a Type II antibody, GA101 appears not to act through CDC and is more potent than the Type I antibody rituximab in inducing cell death via nonclassical induction of apoptosis cytotoxicity, with more direct cytotoxicity and more antibody-dependent cell-mediated cytotoxicity. We evaluated the antitumor activity of GA101 against the human-transformed follicular lymphoma RL model in vivo in severe combined immunodeficient mice (SCID) mice. GA101 induced stronger inhibition of tumor growth than rituximab. Combination of GA101 with cyclophosphamide in vivo confirmed the superiority of GA101 over rituximab. Neutralizing the complement system with cobra venom factor partially impaired the antitumor activity of rituximab, but had no impact on the efficacy of GA101. In vitro GA101 more potently induced cell death of RL cells than rituximab. The expression of a limited number of genes was found to be induced by both antibodies after exposure in vitro. Among these, early growth response 1 and activation transcription factor 3 were confirmed to be increased at the protein level, suggesting a possible role of these proteins in the apoptotic signalling of anti-CD20 antibodies. These data imply that GA101 is superior to rituximab not only as a single agent, but also in combination with chemotherapy. These data suggest the presence of novel signalization pathways activated after exposure to anti-CD20 antibodies.

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“…This Ab targets the CD20 Ag expressed on the surface of malignant and normal B cells. The precise mechanism of action recruited by Rituximab has not yet been defined; however, the cell-killing effector functions, complement-dependent cytotoxicity (CDC) and ADCC, have been implicated (8). To improve the cytotoxic effect of therapeutic IgGs, it is important to first understand the cell-killing mechanism recruited by Abs.…”

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confidence: 99%

Engineered Antibodies with Increased Activity to Recruit Complement

Idusogie¹,

Wong²,

Presta³

et al. 2001

The Journal of Immunology

265

168

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This manuscript describes two sites in a human IgG1 that, when mutated individually or in combination, result in a dramatic increase in C1q binding and complement-dependent cytotoxicity activity. These two residues, K326 and E333, are located at the extreme ends of the C1q binding epicenter in the CH2 domain of a human IgG. A mutation to tryptophan at K326 debilitates Ab-dependent cell-mediated cytotoxicity activity. In addition, substitutions of the residues E333 with serine and of K326 with tryptophan in a human IgG2 confer biological activity in the complement-dependent cytotoxicity assay in which the wild-type IgG2 is inactive. This study reveals that the residues K326 and E333 play a significant role in the control of the biological activity of an IgG molecule and can rescue the activity of an inactive IgG isotype.

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Targeted anti-cancer therapy using rituximab, a chimaeric anti-CD20 antibody (IDEC-C2B8) in the treatment of non-Hodgkin's B-cell lymphoma

Cited by 231 publications

References 0 publications

CD20 antibody (C2B8)-induced apoptosis of lymphoma cells promotes phagocytosis by dendritic cells and cross-priming of CD8+ cytotoxic T cells

CD20 antibody (C2B8)-induced apoptosis of lymphoma cells promotes phagocytosis by dendritic cells and cross-priming of CD8+ cytotoxic T cells

Preclinical Studies on the Mechanism of Action and the Anti-Lymphoma Activity of the Novel Anti-CD20 Antibody GA101

Engineered Antibodies with Increased Activity to Recruit Complement

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