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Immunotherapy of Melanoma Targeting Human High Molecular Weight Melanoma‐Associated Antigen: Potential Role of Nonimmunological Mechanisms
Author(s) -
CHANG CHIENCHUNG,
CAMPOLI MICHAEL,
LUO WEI,
ZHAO WANZHOU,
ZAENKER KURT S.,
FERRONE SOLDANO
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1322.040
Subject(s) - melanoma , immunotherapy , antibody , antigen , immunology , cancer research , monoclonal antibody , immune system , biology , chemistry
A bstract : Induction of humoral anti‐human high molecular weight melanoma‐associated antigen (anti‐HMW‐MAA) immunity following active specific immunotherapy is associated with a statistically significant prolongation of survival in patients with melanoma. This association does not appear to be mediated by immunological mechanisms because anti‐HMW‐MAA antibodies are poor mediators of complement‐ and cell‐mediated cytotoxicity of melanoma cells. Therefore, we have been investigating nonimmunological mechanisms by which anti‐HMW‐MAA antibodies (Abs) affect the biology of melanoma cells. We have demonstrated that anti‐HMW‐MAA mAbs interfere with the interaction of HMW‐MAA with extracellular matrix (ECM) components, a process known to be crucial in the early phase of melanoma metastasis. Furthermore, anti‐HMW‐MAA mAbs appear to block the series of signal transduction events triggered by the interaction of HMW‐MAA with ECM. They include the activation of the family of Rho GTPases, p130 cas , and focal adhesion kinase (FAK). These findings parallel the inhibition of the rat homologue of HMW‐MAA NG2 function by anti‐NG2 antibodies. Taken together, all these results provide a mechanistic explanation not only for the therapeutic effect of anti‐HMW‐MAA antibodies in the treatment of melanoma, but also for the function of HMW‐MAA in the biology of melanoma cells. This information is expected to serve as a useful background to design effective HMW‐MAA‐targeted immunotherapy in patients with melanoma.