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888-mel: A Target for Anti-Tumor Immune Responses

Scientists at the National Institutes of Health (NIH) have developed a human melanoma cell line designated 888-mel from the resected tumor of a 26-year old Caucasian female (patient 888) diagnosed with metastatic melanoma, a frequently terminal cancer. The 888-mel cell line was derived from three separate subcutaneous melanoma lesions on the patient and possesses many characteristics representative of melanoma cell lines developed by these researchers. Most prominently, the 888-mel cell line was used to develop a tumor infiltrating lymphocyte (TIL) culture with high affinity for the tumor cells of patient 888. When the TIL 888 culture was provided as an autologous adoptive immunotherapy treatment to patient 888 in combination with interleukin-2 (IL-2), a complete remission of subcutaneous, lung, and mucosal metastases was observed in the patient for over three years. Since this medical breakthrough, the 888-mel cell line has been well characterized through various laboratory procedures and data involving this cell line has been published as part of numerous articles. Studies have shown that the cell line expresses a variety of tumor associated antigens (TAAs), including tyrosinase, TRP1, TRP2, gp100, MART-1, p15, gp75, mutated beta-catenin, and p53. However, 888-mel does not normally express the MAGE 1, 2, or 3 TAAs. Many melanoma cell lines are HLA-A2 restricted, but the 888-mel cell line is HLA-A2 negative. The HLA class I typing for this cell line is as follows: HLA-A0101, A2402, B55, B62, Cw5201, Cw55, DRbl*1502, DRbl*1610, DQbl*0601, DRb5*0102, DRb5*0203. 888-mel is a validated source of HLA class I peptides utilized in screens that test the reactivity of TIL cultures that are candidates for adoptive immunotherapy trials. 888-mel is also a standard cell line for studying immune responses in cancer, particularly T cell responses. Other experiments show that roscovitine, a cyclin-dependent kinase inhibitor, can induce apoptosis in the 888-mel cell line, so these cells may be useful in various cell death studies.
Patent Abstract: 
: A majority of the cancer vaccines and immunotherapies developed to date have focused on utilizing HLA-A2 restricted tumor epitopes since this HLA allele is largely expressed in the human population. However, therapies restricted to HLA-A2 recognition will not be successful in melanoma patients that do not express this allele. For these patients, additional therapies are needed that are directed against melanoma tumor epitopes presented by different HLA alleles.
Benefits: 
The 888-mel cell line has been well characterized through multiple years of study and is a fundamental cell line for melanoma studies
applications: 
Inventors: 
Steven Rosenberg (NCI)
Internal Laboratory Ref #: 
E-070-2010/0
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