The serologic response of patients with stage II melanoma to allogeneic melanoma cell vaccines

Abstract

Seventeen patients with Stage II malignant melanoma were treated with vaccines prepared from three allogeneic melanoma cell lines in an attempt to induce a humoral immune response against melanoma cell surface antigens. The patients were free of detectable melanoma at the time of vaccination. Vaccines were prepared from three melanoma cell lines that expressed highly restricted melanocyte differentiation antigens. One of these cell lines also expressed an antigen found only on this particular line. The antigens were initially identified by antibodies in autologous serum; they were thus known to be recognized by the human immune system. In addition, two of the cell lines expressed HLA-A, -B, -C, and -DR antigens; no HLA antigens were detectable on the third line. The vaccines were administered sequentially by subcutaneous injection, mixed with bacillus Calmette-Guerin (BCG) or Corynebacterium parvum. The patients' sera were tested for antibodies against cell surface antigens of the vaccine cells in protein A assays and immune adherence assays, and the specificity of observed reactions was defined by absorption tests. Antibodies against alloantigens of the vaccine cells developed in 16 patients and in 15 patients, against antigens related to fetal calf serum in the culture medium. The magnitude of the antibody response to alloantigens varied considerably, with no difference between patients who received BCG or C. parvum with their vaccines. Antibodies against the restricted melanocyte differentiation antigens or the unique melanoma antigen expressed by the vaccine cells were not detected.

Identification of Tumor-Specific Antibodies in Patients With Breast Cancer Vaccinated With Gene-Modified Allogeneic Tumor Cells

“…There are other reports of increased antibody titer to components of FBS after treatment with cell preparations (23)(24)(25). Another report showed a decreased response to the target cells after absorption of serum samples in a plate coated with FBS (32).…”

“…Sera from the first few patients tested exhibited such high binding to tumor cell lysate that we suspected the presence of antibodies to FBS. Previous studies have shown that patients vaccinated with cells grown in media containing FBS develop antibodies to FBS (23)(24)(25). To address this issue, an ELISA was performed with FBS-coated microtiter plates.…”

Vaccines containing purified GM2 ganglioside elicit GM2 antibodies in melanoma patients.

“…Typing of cell lines for expression of cell-surface gangliosides with mAbs 5-3, 3F8, and R24 was performed as described (2,3,5 for high GM2 expression, was established in our laboratory (2). Methods for culturing and harvesting cells for vaccine production have been described (19). Cells were irradiated with 10,000 rads (1 rad = 0.01 gray) from a 'Co source and frozen viable in dimethyl sulfoxide.…”

“…Over the past decade we have immunized sequential groups of melanoma patients with a variety of melanoma cell vaccines (16)(17)(18)(19)(20). These vaccine trials were based on our seriological analysis of the humoral immune response of melanoma patients to cell-surface antigens of autologous and allogeneic melanomas (21), and each vaccine was constructed to contain melanoma surface antigens known to be immunogenic in humans.…”

Gene-based cancer vaccines: an ex vivo approach

“…However, standardization of this approach was not possible due to batch variability and inconsistency of the tumor cell-adjuvant mixture. 33,34 An alternative strategy, that may replace these complex mixtures of tumor cells and bacteria, is the use of gene-modified tumor cells in order to facilitate the start of an immune response. More than 10 years ago, the first papers describing genetic modification of tumor cells with IL-2 and IL-4 were published.…”