theoretically be eligible for immunotherapy. In practice, because some tumors express different tumor antigens, about 60 percent of melanoma patients could be eligible, and lower percentages of patients with other tumor types.
In a preliminary study, patients received three different dosages (30, 100, or 300 micrograms) of MAGE-1 peptide, without adjuvant, subcutaneously, at monthly intervals. After three injections, there was little or no toxicity, no tumor response, and no CTL response. In a second study, patients received either 100 or 300 micrograms of MAGE-3 peptide, again subcutaneously and at monthly intervals. There was no toxicity, but significant tumor response and at least one possible case of CTL response. One melanoma patient showed considerable response by the day of the third injection, but unfortunately died a month later of a brain metastasis. A second patient with 100 metastases around a skin graft showed significant regression after three injections and one year later is tumorfree. A third patient, designated AVL3, had primary melanomas removed in 1990, but in April 1995 had several metastases in the lung; by October 1995 the patient was disease-free, although the tumor subsequently relapsed.
In response to questions from the audience, Dr. van der Bruggen added the following:
Human patients show tumor response but no CTL response, either spleen or peripheral blood; experimental mice show CTL responses but no regression of tumors.
Researchers have not had the opportunity to look for tumor-infiltrating lymphocytes, nor have they looked for antibodies against MAGE-1 and MAGE3, although this is planned.
Researchers cannot explain why regressions are observed only after the third injection. One member of the audience speculated that CTLs have fairly short memory, and since the tumor itself may not be a good source of antigen, multiple injections are needed to maintain a high level of CTLs.
It may be possible to elicit a CD4 restricted response (e.g., to tumor lysate) as a supplement to the initial CD8 response.