What question did this study set out to answer?

To determine the contribution of complement activation and cellular cytotoxic pathways to the therapeutic efficacy of IgG and IgM anti-GD2 monoclonal antibodies in metastatic cancer.

November 15, 2005Cancer Research

Complement-Mediated Mechanisms in Anti-GD2 Monoclonal Antibody Therapy of Murine Metastatic Cancer

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Authors

MIMasaki ImaiKobe University CLCharles LandenUniversity of Iowa RORieko OhtaAichi Cancer Center

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Implication

Preclinical study reveals divergent complement-dependent mechanisms for IgG and IgM anti-GD2 therapy in mice, indicating complement enhances cellular cytotoxicity under limiting conditions.

Key Points

To determine the contribution of complement activation and cellular cytotoxic pathways to the therapeutic efficacy of IgG and IgM anti-GD2 monoclonal antibodies in metastatic cancer.
Treated EL4 metastatic lymphoma-challenged syngeneic mice with anti-GD2 monoclonal antibodies of IgG2a or IgM isotypes.
Assessed antitumor efficacy in mutant mouse strains lacking C3, CR3, or FcgammaR I/III.
Expressed human CD59, an inhibitor of complement-mediated lysis, on EL4 tumor cells to evaluate direct complement-mediated cytotoxicity in vitro and in vivo.
IgG2a therapy protected against metastases primarily via FcgammaR-dependent antibody-dependent cell-mediated cytotoxicity, but C3 deficiency partially reduced protection specifically at limiting antibody doses.
CD59 overexpression successfully prevented complement-mediated cytotoxicity in vitro but had no effect on the therapeutic protection conferred by IgG or IgM in vivo.
IgM therapy was completely ineffective in C3-deficient mice despite CD59 insensitivity, demonstrating that IgM functions via complement-dependent cell-mediated cytotoxicity in vivo.

Cite This Study

Imai et al. (2005) studied this question.

synapsesocial.com/papers/6a1bc21cbc71fb1015a8ee6c https://doi.org/10.1158/0008-5472.can-05-1894

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Implication

Preclinical study reveals divergent complement-dependent mechanisms for IgG and IgM anti-GD2 therapy in mice, indicating complement enhances cellular cytotoxicity under limiting conditions.

Complement-Mediated Mechanisms in Anti-GD2 Monoclonal Antibody Therapy of Murine Metastatic Cancer

Discussion

Member takes

Implication

Key Points

Cite This Study

Complement-Mediated Mechanisms in Anti-GD2 Monoclonal Antibody Therapy of Murine Metastatic Cancer

Discussion

Member takes

Implication

Key Points

Cite This Study

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