7 f) 
Mitchell et al. 
1988 
Allogeneic 
tumor homogenate. 
Detox 
42 
Response in 9/42 
Wallack et al.^* 
1989 
Allogeneic 
viral oncolysate 
39 
Increased disease-free 
interval 
Morton et al . ^ 
1989 
Allogeneic 
tumor cells, 
BCG 
98 
Response in 4/15 
2 3 
Wiseman et al . 
1989 
Autologous 
tumor cells, 
intralymphatic 
32 
Response in 3/32 
Livingston et al.^ 4 
1985 
Autologous 
VSV oncolysate 
13 
No response 
to Class 1 or Class 2 
melanoma antigens 
25' 
2 6 
Livingston et al . 
1987/89 
GM2 ganglioside, 
24 
Serological response 
to GM2 in 17/24 
The data presented show that, despite various methods used in the past to 
vaccinate individual patients, therapeutic efficacy was significant in only a 
minority of patients. However, more recent methods are yielding improved 
results. Therefore, it is logical to pursue newer lines of investigation 
which use the improvements in our conceptual knowledge of the immune system to 
optimize the methods of immunotherapy for metastatic melanoma. 
With the development of antigen-specific monoclonal antibodies, a number of 
proteins, glycoproteins, and glycopeptides were identified as cell-surface 
constituents of human melanoma and candidates for antibody-mediated 
immunotherapy. Prominent among them are the gangliosides GM2, GD2, and GD3. 
When administered with BCG as adjuvant therapy, after pretreatment with low 
dose cyclophosphamide (to counteract suppresser activity) in patients with 
melanoma, vaccines containing purified GM2 elicited production of GM2 
antibodies (25,26). 
The discovery of IL-2 (27) enabled the multi-log in vitro expansion of the 
numbers of the patients' own lymphocytes. In a significant proportion of 
patients, the re infusion of a large number of autologous lymphocytes (LAK 
cells) induced tumor regression. Rosenberg (28-30) initiated a clinical trial 
of LAK cells plus bolus IL-2 (to maintain LAK activity in vivo) in patients 
with a wide variety of tumors. Melanoma was among the most responsive. A 
recent report listed four complete and six partial regressions (21%) in a 
series of 48 evaluable patients (31) . More recently, Rosenberg has recovered 
lymphocytes from tumors (TIL cells) . Re-infusion of TIL cells led to CR and 
PR in approximately 35% of patients (32) . 
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Recombinant DNA Research, Volume 18 
