Degradation of the tumor antigen epitope gp100280 – 288 (YLEPGPVTA) was investigated in the presence of cultured human fibroblasts, and acellular supernatants obtained from these cells; the possible effect of substrate degradation on in vitro immunorecognition was also addressed. In the presence of fibroblasts, gp100280 – 288 was degraded to free amino acids with a half-life of less than 4 min; hydrolysis data support the hypothesis that substrate degradation was mainly caused by the activity of cell-expressed amino- and carboxypeptidases. Gp100280 – 288 was also degraded in the presence of acellular supernatants: under these conditions, the hydrolysis pattern was similar to that observed in the presence of whole cells, but degradation kinetics was slower. As a result of these phenomena, immunorecognition of gp100280 – 288-specific cytotoxic T lymphocyte (CTL) clones was severely hampered, and was totally suppressed after 90 min. In conclusion, the high activity of fibroblast-expressed proteases, and the presence of wide-scope soluble enzymes, may explain, at least in part, the low activity of peptide-based antineoplastic vaccines, as well as the transient effectiveness of subcutaneously administered peptides in general.

Degradation of the tumor antigen epitope gp100280-288 by fibroblast-associated enzymes abolishes specific immunorecognition / Albo, F; Cavazza, Antonella; Giardina, B; Marini, M; Roda, L. G.; Schumacher, R; Spagnoli, G.. - In: BIOCHIMICA ET BIOPHYSICA ACTA. - ISSN 0006-3002. - 1671:(2004), pp. 59-69. [10.1016/j.bbagen.2004.01.006]

Degradation of the tumor antigen epitope gp100280-288 by fibroblast-associated enzymes abolishes specific immunorecognition

CAVAZZA, Antonella;
2004-01-01

Abstract

Degradation of the tumor antigen epitope gp100280 – 288 (YLEPGPVTA) was investigated in the presence of cultured human fibroblasts, and acellular supernatants obtained from these cells; the possible effect of substrate degradation on in vitro immunorecognition was also addressed. In the presence of fibroblasts, gp100280 – 288 was degraded to free amino acids with a half-life of less than 4 min; hydrolysis data support the hypothesis that substrate degradation was mainly caused by the activity of cell-expressed amino- and carboxypeptidases. Gp100280 – 288 was also degraded in the presence of acellular supernatants: under these conditions, the hydrolysis pattern was similar to that observed in the presence of whole cells, but degradation kinetics was slower. As a result of these phenomena, immunorecognition of gp100280 – 288-specific cytotoxic T lymphocyte (CTL) clones was severely hampered, and was totally suppressed after 90 min. In conclusion, the high activity of fibroblast-expressed proteases, and the presence of wide-scope soluble enzymes, may explain, at least in part, the low activity of peptide-based antineoplastic vaccines, as well as the transient effectiveness of subcutaneously administered peptides in general.
2004
Degradation of the tumor antigen epitope gp100280-288 by fibroblast-associated enzymes abolishes specific immunorecognition / Albo, F; Cavazza, Antonella; Giardina, B; Marini, M; Roda, L. G.; Schumacher, R; Spagnoli, G.. - In: BIOCHIMICA ET BIOPHYSICA ACTA. - ISSN 0006-3002. - 1671:(2004), pp. 59-69. [10.1016/j.bbagen.2004.01.006]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/1895547
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