cases, although there was no lack of a humoral immune response to other vaccine 
components (47). Speculation regarding the reasons for the difficulties 
encountered in these attempts to induce an antibody response to class I or class II 
melanoma antigens spawned a range of possibilities including insufficient 
sensitivity of serologic tests, unfavorable antigen presentation in the vaccines, 
genetic restriction of reactivity with melanoma antigens, and suppression of 
antibody production by suppressor cells or anti-idiotypic antibodies. 
With the advent of hybridoma technology, a number of proteins, glycoproteins, 
and glycopeptides were identified as cell-surface constituents of human melanoma 
and candidates for vaccine construction. Prominent among them are the 
gangliosides GM2, GD2, and GD3. Vaccines containing purified GM2 have been 
shown to elicit production of GM2 antibodies in patients with melanoma (48, 49) 
when administered with BCG as adjuvant after pre-treatment with low dose 
cyclophosphamide to counteract suppressor activity. 
Cellular immunity to cancer antigens, as opposed to humoral immunity, has been 
of much interest ever since it was shown in the early 1960’s that specific 
immunity to challenge with chemically induced sarcomas can be transferred in 
the mouse with lymphocytes from immunized donors, but not serum. Defining 
the specificity of cellular immune reactions to cancer has been far more difficult 
than defining the specificity of humoral immune reactions to cancer antigens. To 
this regard, the discovery of the T cell growth factor, interleukin-2, which 
permits culture and cloning of T lymphocytes, has been a major step forward and 
opened a new era in the study of T cell immunity. Cytotoxic T lymphocyte 
clones with restricted reactivity for autologous melanoma have been isolated from 
the blood of patients in several laboratories, and similar results were obtained in 
studies of clones derived from tumor-infiltrated-lymphocytes (TIL) (50). In some 
cases these clones have shown exquisite specificity for autologous melanoma 
(45). In some instances, the presenting MHC molecules could be identified as 
class I molecules by inhibition of lysis with antibodies directed against HLA 
determinants. In the case of the melanoma cell line SK-MEL-29 (patient AV 
from reference 29), established at this institution, at least those antigens are 
recognized by autologous and cytotoxic T cell clones in association with HLA-A2 
(51). 
Both HLA-A2 and HLA-A1 have been identified as restriction elements in other 
melanomas and also sarcomas (52). HLA-A2 expressed on human melanoma 
cells has been shown to present shared melanoma antigens recognized by T cells 
derived from peripheral blood, regional lymph node and tumor infiltrates. Thus, 
HLA-A2 is capable of presenting antigens that are shared among melanoma cells, 
but not apparently expressed by several other cell types. The outstanding 
challenge confronting the field of cellular immunity is the structural definition of 
the targets recognized by cytotoxic cells on human tumor cells. A major advance 
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Recombinant DNA Research, Volume 15 
