γδ T Cell Therapy Development for Neuroblastoma

Human peripheral γδ T cells can induce neuroblastoma (NB) tumor cell lysis, which has become a hot topic in NB therapy.

Introduction to NB

NB is the most common extracranial solid tumor in infancy. It is a malignant tumor of the embryonic sympathetic nervous system caused by neuroblasts (multifunctional sympathetic nerve cells). In the developing embryo, these cells invaginate, migrate along the nerve axis, and distribute in the sympathetic ganglia, adrenal medulla and other parts. The distribution pattern of these cells is related to the location of primary neuroblastoma. The current treatment plan is to combine chemotherapy with surgical resection, external radiation, radionuclide application, high-dose chemotherapy and autologous stem cell transplantation. The introduction of monoclonal antibodies (mAbs) against GD2, an antigen that is abundantly expressed on NB cells, resulted in complete remission or partial tumor response, but only in 1/3 of patients. Therefore, despite the progress of treatment, the prognosis of NB is still poor, and better treatment options are essential.

Fig.1 Glimpse of NB. (Maris, 2010)

γδ T Cell as Foes in NB Development

New strategies for cancer therapy are trying to include the innate anti-tumor defense mechanisms of the immune system. Adoptive transfer of tumor-associated peptide vaccine targeting tumor-specific antigen, natural killer (NK) cell transplantation after autologous stem cell transplantation, and graft anti-tumor effect mediated by donor lymphocyte infusion after allogeneic transplantation are all cell-based anti-tumor strategies. γδ T cells, a subgroup of peripheral blood T cells, are considered to be part of innate immunity. They carry non-pleomorphic cell surface structure-specific receptors and spontaneously cleave target cells without silver-specific activation. In recent years, studies have shown that a large number of peripheral blood mononuclear cells can be obtained by clinical enrichment and/or in vitro amplification. Some studies have shown that the expanded γδ T cells have potential cytotoxicity to several human tumor cell lines including NB.

Fig.2 “Co-stimulation Only” CAR-γδ T cell activation after recognition of two separate tumor-associated molecules. (Parihar, 2017)

Application of γδ T cells in NB

γδ T cells are often detected in tumor infiltrating lymphocytes (TILs), and their role in the treatment of NB has been evaluated by some researchers. In a preliminary study, researchers adoptively transferred in vitro activated γδ T cells in NB patients to assess their safety and possible antitumor effects. The results showed that γδ T cell subsets showed a significant difference when they contacted NB cells. In addition, autologous γδ T cells activated in vitro had good tolerance and could produce an obvious anti-tumor effect.

What Can We Do?

It has been shown that γδ T cells cultured in vitro are particularly suitable for immunotherapy of NB. Since the stem cell apheresis products of most NB patients are CD34⁺ selected, it is easy to obtain a large number of γδ T cells from the CD34 fraction from these patients. In the early stage of immune reconstitution after autologous CD34⁺ selected stem cell transplantation, their re-use after in vitro reproduction may lead to a direct tumor reduction effect or targeted effect on uncommitted γδ T cells. In addition, screening of γδ T cell preparations for the production of angiogenesis and growth-promoting factors after tumor cell activation seems to be an important step in the selection of optimal donor and effector cell types in the near future.

Creative Biolabs is pleased to be your partner in NB treatment research. We can provide you with in vitro culture, validation, modification, and preclinical experiments of γδ T cells, which will help the development of NB immunotherapy. If you want to get more information, please feel free to contact us.

References

1. Maris, J. M. Recent advances in neuroblastoma. New England Journal of Medicine. 2010, 362(23): 2202-2211.
2. Parihar, R. Sensing Bad: Are Co-stimulatory CAR-Expressing γδ T Cells Safer. Molecular Therapy. 2017, 25(5): 1064-1066.