γδ T Cells for Vaccine Development

In recent years, γδ T cells attract a lot of people's attention due to their efficient in vitro tumor killing activities. As a consequence, many researchers are currently studying the tumor killing function of γδ T cells in clinical trials. Although the reported benefits are modest, these studies have revealed that large γδ T-cell infusions were well tolerated. Many studies also demonstrated that γδ T cells not only can be used as effector cells, but also used as a novel cellular vaccine for the treatment of cancer patients. As a leading CRO company, Creative Biolabs provides a range of γδ T cell development services for vaccine development.

γδ T Cells with Antigen-Presentation Function

It has reported that activated γδ T cells team up with αβ T cells and/or DC in the T-cell compartment of secondary lymphoid tissues. Besides, short-term (1–3days) activation of γδ T cells with the phosphor antigens IPP or HMBPP lead to de novo expression (or up-regulation) of cell surface proteins commonly associated with DC, such as antigen presentation (MHC class I and II), co-stimulatory (CD40, CD80, CD86), and adhesion (CD11a, CD11b, CD11c, CD54, CD18) receptors. Thus, it is the possibility that activated (CCR7C) γδ T cells behaved like bona fide antigen-presenting cells (APC).

Protocol for A First-In-Man Clinical Trial with Tumor Antigen-Presenting γδ T-Apc

A simplified procedure of γδ T-APC handling and distribution will benefit clinical trials involving multiple centers.

• After 2 weeks on in vitro culture, tumor antigen-loaded γδ T-APC will be prepared by culturing expanded γδ T cells for 24 h in the presence of defined tumor antigen(s) or tumor cell extracts.
• A personalized immunotherapy protocol will concern the treatment autologous γδ T-cell preparations with extracts from the patient’s tumor cells.
• After washing and reformulation, tumor antigen-loaded γδ T-APC will be divided into individual bolus samples and then frozen in liquid nitrogen for shipment to corresponding cancer clinics.
• The frozen tumor antigen-loaded γδ T-APC samples will then be prepared locally for i.v. infusion into cancer patients based on treatment regimens that require to be defined during clinical trials.

Fig.1 Manufacture of tumor antigen-loaded γδ T-APC for immunotherapy. (Khan, 2014)

Ideally, a single round of cell culture will off enough tumor antigen-loaded γδ T-APC for carrying out the entire round of treatment, which may follow a prime-boost protocol. Importantly, effective cell doses require to be established before being able to apply arithmetic for the production of expanded γδ T cells. A small sample of tumor antigen-loaded γδ T-APC will be retained for quality control that will include sterility, purity, and APC phenotype assessments. What’s more, PBMC from cancer patients yields decreased numbers of expanded γδ T cells or cell preparations containing large (>50%) numbers of non-γδ T cells, indicating that a single magnetic beads purification step could enhance the vaccine function of antigen-loaded γδ T-APC.

Creative Biolabs is a global company that focuses on T cell therapy discovery and development. With our comprehensive platform, we provide a range of γδ T cell-based services to our clients. Please contact us for more information.

References

1. Khan, M., et al. Potential use of [gammadelta] T cell-based vaccines in cancer immunotherapy. Frontiers in immunology. 2014, 5, 512.
2. Khan, M.W.A.; et al. Potential Use of γδ T Cell-Based Vaccines in Cancer Immunotherapy. Frontiers in Immunology. 2014, 5: 512.