Prognostic role of antibody reactivity to melanoma.

Vlock, Daniel R.; DerSimonian, Rebecca; Kirkwood, John M.

doi:10.1172/jci112410

Cited by 14 publications

(7 citation statements)

References 23 publications

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“…The survival of this patient with a high-risk melanoma suggests a favorable prognostic significance of her antibody response. This is consistent with the findings of Jones et al [14], but at variance with results obtained in the setting of a prospective controlled adjuvant trial, where serological reactivity was assessed using a common melanoma-antigen-bearing cell line [32]. At the time of peripheral blood sampling for EBV transformation in this study, serum antibody was no longer detectable in this patient.…”

Section: Discussionsupporting

confidence: 93%

Human IgG and IgM monoclonal antibodies against autologous melanoma produced by Epstein-Barr-virus-transformed B lymphocytes

Kirkwood

Robinson

1990

Cancer Immunol Immunother

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The serum antibody response to human melanoma has prognostic and potential physiological consequences. The specificity of the host B cell antibody response may be an important determinant of disease outcome. We have utilized Epstein-Barr virus (EBV) transformation to analyze the repertory of the host B cell response to melanoma. Production of antibody that binds selectively to autologous (eight cases) or allogeneic (four cases) short-term-cultured melanoma cells was assessed from EBV-transformed B lymphoblastoid cells. Forty-two cultures of EBV-transformed B cells that secreted IgM and 23 that secreted IgG antibodies gave patterns of differential reactivity with autologous or allogeneic melanoma. Antibody-forming B cells persisted in producing melanoma-reactive IgG and IgM for 8-21 weeks. Preselection of B cells by adsorption to tumor cell antigens before transformation enhanced the frequency of antibody secretion. The specificity of the antibody produced by the longest-producing culture appears to be restricted to a subset of melanomas. The patient from whom this tumor-restricted IgG-producing B cell was retrieved was unusual, having had a transient serum IgG of similar specificity, and having manifest a syndrome of vitiligo at the time of her development of serum antimelanoma antibody, followed by disease-free survival of resected recurrent metastatic melanoma to the present (more than 6 years). This study has given support to findings of conventional serology, revealing the production of melanoma-reactive antibody from B cells of patients who have demonstrable serological response to tumor.

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Section: Discussionsupporting

confidence: 93%

Human IgG and IgM monoclonal antibodies against autologous melanoma produced by Epstein-Barr-virus-transformed B lymphocytes

Kirkwood

Robinson

1990

Cancer Immunol Immunother

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“…This report and our previous studies (20,22,23) would suggest an alternative explanation. We have found that the majority of patients with melanoma produce an antibody against their own tumor, however, it is masked by the presence of circulating antigen forming immune complexes.…”

Section: Discussionsupporting

confidence: 69%

“…Serial studies of autologous antibody reactivity, in native and dissociated sera, have demonstrated correlations between clinical course and disease progression (22). In addition, we have found that the presence host-derived antibody reactivity against an allogeneic melanoma cell line is a predictor of eventual disease recurrence (23).…”

Section: Introductionmentioning

confidence: 89%

Isolation and partial characterization of melanoma-associated antigens identified by autologous antibody.

Vlock¹,

Scalise²,

Meglin³

et al. 1988

J. Clin. Invest.

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The study of the autologous immune response to cancer avoids the difficulties encountered in the use of xenoantisera and may identify antigens of physiological relevance. However, the low titer and incidence of autologous antibody to melanoma have hampered further evaluation. By utilizing acid dissociation and ultrafiltration of serum, we have been able to augment the detectable autologous immune response to melanoma in the majority of patients studied. In autologous system Y-Mel 84:420, serum S150 demonstrated a rise in titer from 1:32 in native sera to 1:262,044 after dissociation. The antigen detected by S150 was found to be broadly represented on melanoma, glioma, renal cell carcinoma, neuroblastoma, and head and neck carcinoma cell lines. It did not react with bladder or colon carcinoma, fetal fibroblasts, pooled platelets, lymphocytes and red blood cells, or autologous cultured lymphocytes. Using polyacrylamide gel electrophoresis, S150 detects a 66,000-mol wt antigen in spent tissue culture media and serum ultrafiltrate. In cell lysate two bands between 20,000 and 30,000 mol wt are detected by S150. The 66,000-mol wt antigen is sensitive to trypsin digestion and but is resistant to pepsin and heat inactivation. Exposure of spent media to trypsin results in the development of a 24,000-mol wt band that appears to correspond to the antigen detected in the cell lysate. The difference between the antigens detected in the cell lysate as compared with spent media and serum ultrafiltrate may be due to degradation during cell lysis. We conclude that melanoma-associated antigens are present in the serum of patients with melanoma and are shed or secreted by their tumor cells.

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“…We demonstrated that, in a method described by Sjogren et al [18], dissociation of immune complexes in melanoma and SCCHN [11,23] augments autologous antibody reactivity in the majority of cases studied. Further studies in melanoma have shown correlations between autologous antibody titers, clinical course and prognosis [19][20][21]. In SCCHN native sera from eight patients were subjected to acid dissociation and ultrafiltration of sera.…”

Section: Introductionmentioning

confidence: 99%

Serial studies of autologous antibody reactivity to squamous cell carcinoma of the head and neck

Vlock

Arnold

Humpierres

et al. 1992

Cancer Immunol Immunother

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In previous studies we evaluated the incidence and specificity of autologous antibody reactivity against squamous cell carcinoma of the head and neck (SCCHN). We were able to demonstrate that autologous antibody reactivity is present in native sera but was usually of too low a titer to allow further analysis. Dissociation of immune complexes by acidification and ultrafiltration of serum augmented autologous antibody reactivity in nine out of nine autologous systems tested. Native antibody and antibody derived from immune complexes produced by the host and reactive with autologous tumor cells may be directed against physiologically relevant antigens. Therefore, correlations of antibody titers with clinical course may provide insight into the nature of the host response to cancer. In the present analysis, serological studies of six patients with SCCHN were performed with serum samples obtained over many months. Results of serial serological assays were correlated to tumor progression and clinical course. Fluctuations in autologous antibody reactivity were noted over time. In four cases, rises in autologous antibody titers preceded the clinical diagnosis of recurrence by several months. Drops in autologous antibody reactivity were noted in two cases following surgery or radiation therapy. In two cases of long-term survivors, no correlation between antibody reactivity and clinical course was noted. Specificity analysis of the six autologous systems demonstrated reactivity against autologous and allogeneic SCCHN as well as melanoma cell lines. These sera did not react with glioma, neuroblastoma, renal cell, breast, bladder and colon carcinoma cell lines nor with fetal calf serum, pooled lymphocytes, red blood cells and platelets. Autologous serial serological studies may provide a means by which to evaluate the host/tumor relationship in patients with SCCHN.

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Prognostic role of antibody reactivity to melanoma.

Cited by 14 publications

References 23 publications

Human IgG and IgM monoclonal antibodies against autologous melanoma produced by Epstein-Barr-virus-transformed B lymphocytes

Human IgG and IgM monoclonal antibodies against autologous melanoma produced by Epstein-Barr-virus-transformed B lymphocytes

Isolation and partial characterization of melanoma-associated antigens identified by autologous antibody.

Serial studies of autologous antibody reactivity to squamous cell carcinoma of the head and neck

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