Adoptive transfer of an anti-MART-127–35-specific CD8+ T cell clone leads to immunoselection of human melanoma antigen-loss variants in SCID mice
✍ Scribed by Francesco Lozupone; Licia Rivoltini; Francesca Luciani; Massimo Venditti; Luana Lugini; Agata Cova; Paola Squarcina; Giorgio Parmiani; Filippo Belardelli; Stefano Fais
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 491 KB
- Volume
- 33
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
The identification of appropriate mouse models could be useful in carefully evaluating the actual role of the in vivo development of antigen‐loss variants during antigen‐specific vaccine therapy of human tumors. In this study we investigated the level of efficacy of a MART‐1/Melan‐A‐specific CD8^+^ T cell clone against its autologous melanoma in a severe combined immunodeficiency (SCID) mouse model, in which the tumor cells expressed in vivo heterogeneous and suboptimal levels of MART‐1. The subcutaneous co‐injection of the MART‐1/Melan‐A‐reactive T cell clone A42 with MART‐1/Melan‐A^+^ autologous human melanoma cells into SCID mice caused a total inhibition of tumor growth. However, the systemic treatment with A42 clone lymphocytes resulted inonly 50–60% inhibition of tumor growth, although the T cell clone targeted the tumors and the MART‐1^+^ cells virtually disappeared from the tumors. This study suggests that an immunotherapybased on the expansion of an antigen‐specific T cell clone generated in vitro is highly efficient in abolishing tumor growth when the target antigen is fully expressed, but leads to in vivo__immunoselection of antigen‐loss variants in the presence of suboptimal levels of antigen expression. Furthermore, this work shows that human tumors/SCID mouse models may be useful in evaluating the__in vivo efficacy of adoptive immunotherapies.