One-stop NKT TCR-γδ T Cell Development Services

All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.

With extensive experience in cellular therapy development services, Creative Biolabs extends its efforts to γδ T cell therapy development services. Now we are dedicated to discovering, developing and manufacturing invariant natural killer T (NKT)-TCR engineered γδ T cell services to satisfy your research demands.

NKT Cells and TCR

NKT cells are a specialized subset of T cells that share morphological and functional characteristics of both NK cells and T cells. Instead of interacting with peptides presented by MHC molecules, the TCRs expressed by NKT cells recognize glycolipids presented by CD1d, a non-polymorphic MHC-I-like molecule. NKT cells have the capacity to mount strong anti-tumor responses. They are potent immune regulators since they can rapidly produce either T helper (TH)1-, TH2-, TH17-, T regulatory (Treg)-, or follicular helper (TFH)-cell-associated cytokines. NKT cells have the capacity to mount strong anti-tumor responses and have thus become a major focus in the development of effective cancer immunotherapy.

The majority of invariant NKT cells (type I) have been traditionally defined by the expression of an invariant TCR α-chain (Vα14-Jα18 in mice or Vα24-Jα18 in humans) and TCR β-chains (TRBV1, TRBV13, and TRBV29 in mice, TRBV25 in humans). The TCRs present on invariant NKT cells recognize the antigen alpha-galactosylceramide (alpha-GalCer). In addition, type II NKT cells are described with a more diverse and less well-defined TCR repertoire recognizing non-α-GalCer molecules (primarily sulfatide) presented by CD1d molecules.

Fig.1 NKT cell classification. (Cui, 2019)

The TCR-engineered T cells express tumor antigen-specific receptors with α and β chains which are produced from high-quality and high-avidity antigen-specific T-cell clones. The use of iNKT TCR in cancer immunotherapy has shown promising results but remains some limitations. Transfer of TCRs derived from iNKT cells into γδ T cells has been used to overcome the restrictions inherent in αβTCR gene transfer, such as MHC restriction. Since γδ T cells do not have αβ chains, transfection of iNKT α and β chains into γδ T cells will not result in mispaired receptors. Research indicated that γδ T cells expressing iNKT cell-derived TCRs led to γδ T cells expansion in the presence of glycolipids and an increase of cytotoxicity against the CD1d expressing leukemia cell line. iNKT TCR-transduced γδ T cells retain their γδ TCR expression and are able to respond to iNKT and γδ T cell ligands, rendering them bi-potential innate lymphocytes.

Fig.2 Transferring NKT-TCRs into γδ T cells. (Fisher, 2018)

Creative Biolabs has developed a state-of-art γδ T cells platform to generate γδ T cells expressing NKT cell-derived TCRs. The workflow mainly includes several steps as follows.

Prepare NKT cells and γδ T cells
Clone NKT TCR into a plasmid vector
Transfer NKT TCR into γδ T cells
Bis-specific response analysis (NKT TCR-γδ T cells are treated with αGalCer or zoledronic acid)

Related Sevices

The TCR-genetically engineered immune cells have produced effective immunity during cancer treatment which has been validated in preclinical and clinical trials. Creative Biolabs expands our capabilities to γδ T cells expressing NKT cell-derived TCRs. With advanced technologies and rich experience, we provide one-stop services for the development of NKT TCR-γδ T cells. Please don't hesitate to contact us to learn how we can be involved in your projects.

References

Cui, Y.; Wan, Q. NKT cells in neurological diseases. Frontiers in cellular neuroscience. 2019, 13: 245.
Fisher, J.; Anderson, J. Engineering approaches in human gamma delta T cells for cancer immunotherapy. Frontiers in immunology. 2018, 9: 1409.