Selective bispecific T cell recruiting antibody and antitumor activity of adoptive T cell transfer.
J Natl Cancer Inst
; 107(1): 364, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25424197
ABSTRACT
BACKGROUND:
One bottleneck for adoptive T cell therapy (ACT) is recruitment of T cells into tumors. We hypothesized that combining tumor-specific T cells, modified with a marker antigen and a bispecific antibody (BiAb) that selectively recognizes transduced T cells and tumor cells would improve T cell recruitment to tumors and enhance therapeutic efficacy.METHODS:
SV40 T antigen-specific T cells from T cell receptor (TCR)-I-transgenic mice were transduced with a truncated human epidermal growth factor receptor (EGFR) as a marker protein. Targeting and killing by combined ACT and anti-EGFR-anti-EpCAM BiAb therapy was analyzed in C57Bl/6 mice (n = six to 12 per group) carrying subcutaneous tumors of the murine gastric cancer cell line GC8 (SV40(+) and EpCAM(+)). Anti-EGFR x anti-c-Met BiAb was used for targeting of human tumor-specific T cells to c-Met(+) human tumor cell lines. Differences between experimental conditions were analyzed using the Student's t test, and differences in tumor growth with two-way analysis of variance. Overall survival was analyzed by log-rank test. All statistical tests were two-sided.RESULTS:
The BiAb linked EGFR-transduced T cells to tumor cells and enhanced tumor cell lysis. In vivo, the combination of ACT and Biab produced increased T cell infiltration of tumors, retarded tumor growth, and prolonged survival compared with ACT with a control antibody (median survival 95 vs 75 days, P < .001). In human cells, this strategy enhanced recruitment of human EGFR-transduced T cells to immobilized c-Met and recognition of tyrosinase(+) melanoma cells by TCR-, as well as of CEA(+) colon cancer cells by chimeric antigen receptor (CAR)-modified T cells.CONCLUSIONS:
BiAb recruitment of tumor-specific T cells transduced with a marker antigen to tumor cells may enhance efficacy of ACT.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
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Receptores de Antígenos de Linfócitos T
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Linfócitos T
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Moléculas de Adesão Celular
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Transferência Adotiva
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Proteínas Proto-Oncogênicas c-met
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Receptores ErbB
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Antígenos de Neoplasias
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article