The availability of a functional tumor targeting T-cell repertoire determines the anti-tumor efficiency of combination therapy with anti-CTLA-4 and anti-4-1BB antibodies.

It has previously been found that combination therapy with anti-CTLA-4 and anti-4-1BB antibodies may enhance tumor immunity. However, this treatment is not efficient against all tumors, and it has been suggested that variations in tumor control may reflect differences in the immunogenicity of differ...

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Autores principales:	Benjamin A H Jensen, Sara R Pedersen, Jan P Christensen, Allan R Thomsen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1d498ace87d84a57ab27548affe0c64a
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spelling	oai:doaj.org-article:1d498ace87d84a57ab27548affe0c64a2021-11-18T07:41:52ZThe availability of a functional tumor targeting T-cell repertoire determines the anti-tumor efficiency of combination therapy with anti-CTLA-4 and anti-4-1BB antibodies.1932-620310.1371/journal.pone.0066081https://doaj.org/article/1d498ace87d84a57ab27548affe0c64a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23785471/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203It has previously been found that combination therapy with anti-CTLA-4 and anti-4-1BB antibodies may enhance tumor immunity. However, this treatment is not efficient against all tumors, and it has been suggested that variations in tumor control may reflect differences in the immunogenicity of different tumors. In the present report, we have formally tested this hypothesis. Comparing the efficiency of combination antibody therapy against two antigenically distinct variants of the B16.F10 melanoma cell line, we observed that antibody therapy delayed the growth of a variant expressing an exogenous antigen (P<0.0001), while this treatment failed to protect against the non-transfected parental line (P = 0.1850) consistent with published observations. As both cell lines are poorly immunogenic in wild type mice, these observations suggested that the magnitude of the tumor targeting T-cell repertoire plays a major role in deciding the efficiency of this antibody treatment. To directly test this assumption, we made use of mice expressing the exogenous antigen as a self-antigen and therefore carrying a severely purged T-cell repertoire directed against the major tumor antigen. Notably, combination therapy completely failed to inhibit tumor growth in the latter mice (P = 0.8584). These results underscore the importance of a functionally intact T-cell population as a precondition for the efficiency of treatment with immunomodulatory antibodies. Clinically, the implication is that this type of antibody therapy should be attempted as an early form of tumor-specific immunotherapy before extensive exhaustion of the tumor-specific T-cell repertoire has occurred.Benjamin A H JensenSara R PedersenJan P ChristensenAllan R ThomsenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e66081 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Benjamin A H Jensen Sara R Pedersen Jan P Christensen Allan R Thomsen The availability of a functional tumor targeting T-cell repertoire determines the anti-tumor efficiency of combination therapy with anti-CTLA-4 and anti-4-1BB antibodies.
description	It has previously been found that combination therapy with anti-CTLA-4 and anti-4-1BB antibodies may enhance tumor immunity. However, this treatment is not efficient against all tumors, and it has been suggested that variations in tumor control may reflect differences in the immunogenicity of different tumors. In the present report, we have formally tested this hypothesis. Comparing the efficiency of combination antibody therapy against two antigenically distinct variants of the B16.F10 melanoma cell line, we observed that antibody therapy delayed the growth of a variant expressing an exogenous antigen (P<0.0001), while this treatment failed to protect against the non-transfected parental line (P = 0.1850) consistent with published observations. As both cell lines are poorly immunogenic in wild type mice, these observations suggested that the magnitude of the tumor targeting T-cell repertoire plays a major role in deciding the efficiency of this antibody treatment. To directly test this assumption, we made use of mice expressing the exogenous antigen as a self-antigen and therefore carrying a severely purged T-cell repertoire directed against the major tumor antigen. Notably, combination therapy completely failed to inhibit tumor growth in the latter mice (P = 0.8584). These results underscore the importance of a functionally intact T-cell population as a precondition for the efficiency of treatment with immunomodulatory antibodies. Clinically, the implication is that this type of antibody therapy should be attempted as an early form of tumor-specific immunotherapy before extensive exhaustion of the tumor-specific T-cell repertoire has occurred.
format	article
author	Benjamin A H Jensen Sara R Pedersen Jan P Christensen Allan R Thomsen
author_facet	Benjamin A H Jensen Sara R Pedersen Jan P Christensen Allan R Thomsen
author_sort	Benjamin A H Jensen
title	The availability of a functional tumor targeting T-cell repertoire determines the anti-tumor efficiency of combination therapy with anti-CTLA-4 and anti-4-1BB antibodies.
title_short	The availability of a functional tumor targeting T-cell repertoire determines the anti-tumor efficiency of combination therapy with anti-CTLA-4 and anti-4-1BB antibodies.
title_full	The availability of a functional tumor targeting T-cell repertoire determines the anti-tumor efficiency of combination therapy with anti-CTLA-4 and anti-4-1BB antibodies.
title_fullStr	The availability of a functional tumor targeting T-cell repertoire determines the anti-tumor efficiency of combination therapy with anti-CTLA-4 and anti-4-1BB antibodies.
title_full_unstemmed	The availability of a functional tumor targeting T-cell repertoire determines the anti-tumor efficiency of combination therapy with anti-CTLA-4 and anti-4-1BB antibodies.
title_sort	availability of a functional tumor targeting t-cell repertoire determines the anti-tumor efficiency of combination therapy with anti-ctla-4 and anti-4-1bb antibodies.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/1d498ace87d84a57ab27548affe0c64a
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The availability of a functional tumor targeting T-cell repertoire determines the anti-tumor efficiency of combination therapy with anti-CTLA-4 and anti-4-1BB antibodies.

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