Association of HLA phenotype with response to active specific immunotherapy of melanoma

Only a proportion of patients with disseminated melanoma who were immunized successfully with a therapeutic melanoma vaccine (theraccine) had a major clinical response. We investigated whether there was a correlation between their HLA phenotypes and the likelihood of a clinical response.

Seventy patients with disseminated melanoma who were treated with melanoma theraccine were HLA-typed serologically. The two melanoma cell lines used in the theraccine also were typed by serology and cDNA probes (for class II). Results were analyzed to see whether any alleles were present or absent in responders consistently.

The HLA class I alleles A2 (and the cross-reacting A28), B12 (and its split B44 and B45), and C3 were found to be associated with clinical remission. The effects of these alleles on response were apparent when two or more of the alleles were analyzed together. There was a 38% response rate in those 24 patients with two or three of the alleles compared with 20% in the group as a whole.

These data support two distinct possibilities between which we cannot yet distinguish. Responses may be more likely when there is a close match between the HLA molecules in the theraccine and the patients' own molecules. Alternatively, certain types of HLA class I molecules present in the patients may facilitate rejection of autochthonous melanomas by efficiently presenting melanoma-associated antigens to cytotoxic T cells.