Generation of human autologous melanoma-specific cytotoxic T-cells using HLA-A2-matched allogeneic melanomas.
Autologous tumor-specific cytotoxic T-lymphocytes (CTLs), generated by repeated stimulation with autologous melanoma and expanded in interleukin 2, are major histocompatibility complex restricted. These CTLs recognize a common tumor-associated antigen in the presence of HLA class I determinants, suggesting that allogeneic melanomas which express the restricting HLA-A region antigen could substitute for the autologous tumor in the generation of CTLs. This was investigated in the HLA-A2 system. Four T-cell lines were established by stimulation of lymphocytes with either autologous tumor or an HLA-A2-matched allogeneic melanoma. Allogeneic stimulated CTLs specifically lysed the autologous tumor and demonstrated an identical pattern of HLA-A2 restriction, when compared to the autologous stimulated CTLs. Lysis by the allogeneic stimulated CTLs was blocked by a monoclonal antibody to HLA class I antigens; lysis was also inhibited by both autologous tumor or HLA-A2 allogeneic melanomas when evaluated in cold target competition studies. The allogeneic stimulated CTLs proliferated in response to both autologous tumor and HLA-A2 melanomas, but not in response to HLA-A2 nonmelanomas. By phenotypic analysis these CTLs were CD3+ and predominantly CD8+ cells. We conclude that autologous tumor-specific CTLs can be generated using HLA-A region-matched allogeneic melanomas for stimulation. Since established, HLA-typed melanoma tumor lines can be used in the absence of autologous tumor; this procedure can be applied clinically to a broad patient population and may prove useful in the adoptive immunotherapy of melanoma.
Crowley
N J
NJ
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710.
Slingluff
C L
CL
Darrow
T L
TL
Seigler
H F
HF
D015551:Autoimmunity; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015234:HLA-A Antigens / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015234:HLA-A Antigens; D006681:HLA-D Antigens