αβ TCR-Engineered γδ T Cells Development Services

Cellular immunotherapy is a promising strategy for the treatment of cancer. However, the adoptive transfer of sufficient numbers of antigen-specific T cells requires complex isolation methods and laborious and time-consuming tissue culture procedures. Under such circumstances, the development of αβ TCR-engineered γδ T cells as an alternative method has shown its efficiency. As an industry-leading company, Creative Biolabs has a professional expert team to provide high-quality αβ TCR-engineered γδ T cells development services.

Why Adoptive γδ T Cells for Cancer Therapy?

Most current immunotherapeutic approaches aim at inducing antitumor responses via stimulation of the adaptive immune system, which is dependent on MHC-restricted αβ T cells. Most current adoptive T cell therapies for cancer have employed αβ T cells with MHC-restricted TCRs or MHC-independent CARs. Several lines of evidence suggest that T cell-based adoptive immunotherapy forms an attractive approach for the treatment of various malignancies. Infusion of donor lymphocytes for the treatment of hematological malignancies has been shown to result in 20-80% complete remissions depending on the nature of leukemia. Successful adoptive immunotherapy based on the adoptive transfer of ex vivo-expanded tumor-infiltrating lymphocytes in conditioned recipients has been demonstrated for metastatic melanoma.

Fig.1 Genetic modification of γδ T cells for adoptive therapy approaches to cancer. (Legut, 2015)

Introduction to αβ TCR-Engineered γδ T Cells Development

The successful application of T cell-based immunotherapeutic applications depends on the availability of large numbers of T cells with the desired Ag specificity and phenotypic characteristics. The engineering of TCR-transferred T lymphocytes is an attractive strategy to obtain sufficient T cells with an Ag specificity of choice. However, the complex isolation methods of T cells with the desired Ag specificity and laborious and time-consuming tissue culture procedures are likely to prevent the widespread application of these approaches. Recent reports have demonstrated that these difficulties can be overcome by an alternative strategy, namely the transfer of T cell specificity by the genetic introduction of TCR α- and β-chains into T lymphocytes. Because T cell specificity is exclusively determined by the TCR, the genetic transfer of TCR chains to T cells generates T cells with the desired Ag specificity. The potential in vivo efficacy of TCR-transferred T cells has been demonstrated in mouse models. As shown in these various murine models, TCR-transferred T cells can be activated by Ag in vivo, home to effector sites, and can break tolerance against defined self Ags. Importantly, TCR gene transfer can largely halt tumor progression in a spontaneous prostate carcinoma model, under conditions in which vaccination is without effect.

Services at Creative Biolabs

As an industry-leading global CRO company, Creative Biolabs has been focusing on cellular immunotherapy for years. Extensive experience makes us capable of satisfying global researchers’ any puzzles of γδ T cells development services.

• αβ TCR Generation for Engineered γδ T Cell

A potential disadvantage of TCR gene transfer to other αβ T cells is the formation of mixed TCR dimers. Chains of the introduced TCR can pair with the endogenous TCR chains naturally expressed by the TCR-transferred T cells. To completely prevent the formation of mixed TCR dimers by TCR gene transfer, a novel strategy to redirect peripheral blood-derived γδ T cells by αβTCR gene transfer is proposed. γδ T cells comprise 1% to 10% of peripheral blood T cells and express a γδ TCR that cannot exchange chains with αβTCRs. Thus, αβTCR transfer to γδ T cells can generate highly efficient redirected effector T cells, which do not express the potentially detrimental mixed TCR dimers, making them suitable for application in cellular immunotherapy.

• αβ TCR Transduction for Engineered γδ T Cell

An effective method to obtain large numbers of T cells with a defined antigen specificity is the retroviral transfer of a T-cell receptor (TCR). Because T-cell specificity is exclusively determined by the TCR, T-cell specificity can be functionally transferred to other T lymphocytes by retroviral TCR gene transfer.

• Validation of αβ TCR-γδ T Cells

Validation is also an important role during αβ TCR-engineered γδ T cells development process. Creative Biolabs provides comprehensive validation services including viability tests and functional tests. Our platform with advanced technology will dispel any puzzles of our global customers.

Please feel free to contact us for detailed information.

Reference

1. Legut, M.; et al. The promise of gammadelta T cells and the gammadelta T cell receptor for cancer immunotherapy. Cell Mol Immunol. 2015, 12(6): 656-68.