1.0 
OBJECTIVE 
To immunize HLA-A2-positive melanoma patients with HLA-A2 matched 
allogeneic melanoma cells that have been altered to secrete interleukin-2. The 
following will be evaluated: 
1.1 Toxicity of immunization 
1.2 Evidence for induction of humoral and cellular immunity 
1 . 3 Anti-tumor effects 
2.0 BACKGROUND 
2.1 Malignant melanoma . 
Annually more than 32,000 cases of melanoma are diagnosed in the United 
States, resulting in greater than 8000 deaths (3). Current systemic therapy for 
metastatic melanoma is inadequate. Dacarbazine (DTIC) is the most active single 
chemotherapeutic agent and is widely employed in the treatment of patients with 
metastatic disease, with response proportions ranging from 14-20% (4-8). 
Clinically meaningful regression of visceral metastases is uncommon. The 
nitrosoureas have also been used with equally disappointing results (4-8). 
Combination chemotherapy has not clearly improved the response proportion 
observed with single agent therapy, and has greater toxicity (6-8). 
The failure of conventional chemotherapeutic agents to impact on the treatment 
of metastatic melanoma has prompted the use of biological response modifiers in 
clinical trials. Studies have used interleukin-2 (IL-2) with or without LAK cells 
(1,2), interferon (9), and monoclonal antibodies (10), with response proportions 
ranging from 19-23%. These response proportions are modest in current 
treatment regimens employed, with sometimes considerable toxicity. 
2.2 Vaccination Studies 
Every decade since the turn of the century has seen efforts to develop cancer 
vaccines, and these have taken the form of autologous or allogeneic fresh tumor 
tissues, cultured tumor cells, or tumor cells modified by chemicals, enzymes or 
viral infection. Malignant melanoma has been the leading type of cancer by far in 
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