Targeted Therapeutics in Melanoma by Thomas F. Gajewski & F. Stephen Hodi

Author:Thomas F. Gajewski & F. Stephen Hodi
Language: eng
Format: epub
Publisher: Springer New York, New York, NY

Multiplicity of Antigens on Melanomas

It is obvious that melanoma cells carry multiple HLA/peptide associations that can be recognized by autologous T cells. Many of these antigens are immunogenic in vivo, i.e. induce spontaneous anti-tumor T cell responses. Figure 11.3 illustrates this point, with four melanoma lines and their sets of antigens recognized by autologous CTL clones. We believe that these sets correspond to antigens recognized by spontaneous anti-melanoma CTL responses of the patients because the CTL clones were obtained simply through stimulation of blood mononuclear cells with autologous melanoma cells and T cell growth factors, which in our hands is insufficient for de novo CTL priming. Thus, we think that all these melanoma-specific CTL were primed in vivo, and restimulated in vitro. Comparing the four melanomas, it appears that immunogenicity can result mostly from either mutated antigens (MZ7-MEL [93] or LB33-MEL), or antigens encoded by cancer-germline genes (MZ2-MEL). It is perhaps not coincidental that only one of the 28 identified antigens presented in Fig. 11.3 is coded by a gene (PRAME) that is expressed by normal cells other than male germline cells or melanocytes. Spontaneous T cell responses against the “overexpressed” tumor antigens are probably prevented by natural immunological tolerance.

Fig. 11.3Multiple antigens recognized by CTL on human melanomas. The indicated HLA/peptide combinations were identified with autologous CTL clones obtained from MLTC experiments. On LB33-MEL at least two different antigens were not identified, they are indicated with question marks. MUT stands for various ubiquitously expressed, mutated genes

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