pubmed.ncbi.nlm.nih.gov

Rebalancing immune specificity and function in cancer by T-cell receptor gene therapy - PubMed

Review

Rebalancing immune specificity and function in cancer by T-cell receptor gene therapy

Akshata Udyavar et al. Arch Immunol Ther Exp (Warsz). 2010 Oct.

Abstract

Adoptive immunotherapy with tumor-specific T lymphocytes has demonstrated clinical benefit in some cancers, particularly melanoma. Yet isolating and expanding tumor-specific cells from patients is challenging and there is limited ability to control T-cell affinity and response characteristics. T-cell receptor (TCR) gene therapy, in which T lymphocytes for immunotherapy are redirected using an introduced rearranged TCR, has emerged as an important alternative. Successful TCR gene therapy requires consideration of a number of issues, including TCR specificity and affinity, optimal gene therapy constructs, types of T cells administered, and the survival and activity of the modified cells. In this review we highlight the rationale for and experience with TCR gene therapy as well as new approaches to enhancing it.

PubMed Disclaimer

Cited by

New approaches for the immunotherapy of acute myeloid leukemia.
Geiger TL, Rubnitz JE. Geiger TL, et al. Discov Med. 2015 Apr;19(105):275-84. Discov Med. 2015. PMID: 25977190 Free PMC article. Review.
How (specific) would like your T-cells today? Generating T-cell therapeutic function through TCR-gene transfer.
Daniel-Meshulam I, Ya'akobi S, Ankri C, Cohen CJ. Daniel-Meshulam I, et al. Front Immunol. 2012 Jul 6;3:186. doi: 10.3389/fimmu.2012.00186. eCollection 2012. Front Immunol. 2012. PMID: 22783259 Free PMC article.
Human leucocyte antigen class I-redirected anti-tumour CD4⁺ T cells require a higher T cell receptor binding affinity for optimal activity than CD8⁺ T cells.
Tan MP, Dolton GM, Gerry AB, Brewer JE, Bennett AD, Pumphrey NJ, Jakobsen BK, Sewell AK. Tan MP, et al. Clin Exp Immunol. 2017 Jan;187(1):124-137. doi: 10.1111/cei.12828. Epub 2016 Nov 14. Clin Exp Immunol. 2017. PMID: 27324616 Free PMC article.

References

1. Alli R, Nguyen P, Geiger TL. Retrogenic modeling of experimental allergic encephalomyelitis associates T cell frequency but not TCR functional affinity with pathogenicity. J Immunol. 2008;181:136–145. - PMC - PubMed
1. Amrani A, Verdaguer J, Serra P, Tafuro S, Tan R, Santamaria P. Progression of autoimmune diabetes driven by avidity maturation of a T-cell population. Nature. 2000;406:739–742. - PubMed
1. Arstila TP, Casrouge A, Baron V, Even J, Kanellopoulos J, Kourilsky P. A direct estimate of the human alphabeta T cell receptor diversity. Science. 1999;286:958–961. - PubMed
1. Atanackovic D, Cao Y, Kim JW, Brandl S, Thom I, Faltz C, Hildebrandt Y, Bartels K, de Weerth A, Hegewisch-Becker S, et al. The local cytokine and chemokine milieu within malignant effusions. Tumour Biol. 2008;29:93–104. - PubMed
1. Avril MF, Charpentier P, Margulis A, Guillaume JC. Regression of primary melanoma with metastases. Cancer. 1992;69:1377–1381. - PubMed

Rebalancing immune specificity and function in cancer by T-cell receptor gene therapy - PubMed