Immunophenotype of regionally recurrent melanoma of the extremity in patients before isolated limb infusion (ILI)

Abstract

8052 Background: ILI is an effective, though palliative, treatment for patients with regionally recurrent melanoma of the extremity. Tumor-associated antigens such as the Cancer Testis (CT) antigens and melanocyte differentiation antigens (MDAs) have been used successfully as targets for vaccine-based immunotherapy trials in patients with recurrent melanoma. Little is known about expression of these antigens in patients with regional disease. Methods: Samples of regionally recurrent melanoma were obtained from patients prior to ILI as part of an ongoing clinical trial. 22 available samples were formalin-fixed, paraffin-embedded and analyzed by IHC for the following antigens (using the following monoclonal antibodies): CT antigens (MAGE-A1 [MA454], MAGE-A3 [M3H67], MAGE-A4 [57B], NY-ESO-1 [E978], CT7/MAGE-C1 [CT-33], GAGE) and MDAs (gp100 [HMB45], Melan-A/MART-1 [A103], tyrosinase [T311]). The presence of antibodies to CT antigens was analyzed by ELISA. Results: The antigen expression profile was as follows (positive/total): MAGE-A1 9/22 (41%); MAGE-A3 13/22 (59%), MAGE-A4 11/22 (50%), CT7 14/22 (64%), NY-ESO-1 8/22 (36%), GAGE 12/22 (55%), Melan-A 20/22 (91%), tyrosinase 20/22 (91%), gp100 19/22 (86%). The expression pattern was homogeneous for the vast majority of MDAs and for most CT antigens. No serologic response to any of the tested CT antigens was found in any of the patients. Conclusions: Regionally recurrent melanoma exhibits a homogeneous expression of melanocyte differentiation and CT antigens indicating expression similar to distant metastases. Despite the often prolonged course of patients with regionally recurrent disease, there is no evidence of an effective immune response to CT antigens. No significant financial relationships to disclose.