Applications of Cell Surface Engineering in Cancer Cells

Cancer cells mostly derive from genetic changes and differ from normal cells in the body in many ways, including continuing to grow, immortality, and having the ability to metastasize to other regions of the body. The surface engineering of cancer cells has been leveraged for both therapeutic and diagnostic purposes.

Cancer Cell Surface Engineering for Enhanced Tumor Vaccine

The use of whole killed cancer cells, which provide a comprehensive source of tumor-associated antigens (TAAs), is a cancer vaccine strategy that has shown promising outcomes in preclinical and clinical settings. While these cells have delivered encouraging results in clinical trials, enhancement of the immunogenicity of these vaccines is still required to further induce potent protective immunity. The cell surface engineering of tumor cells with various immune modifiers and costimulatory agents can enhance the immunogenicity of the vaccine compared to providing a soluble form of the adjuvant.

• Case 1

Some researchers have covalently conjugated immunostimulatory CpG oligodeoxynucleotides (ODN) to apoptotic tumor cells and examined their ability to induce TAA-specific immune responses. Results indicate that CpG conjugation is useful in multiple cancer models. It can enhance the uptake of cell-based vaccines by dendritic cells (DCs), regulate co-stimulatory molecule expression, and promote the production of immunostimulatory cytokines. Moreover, vaccination with CpG-conjugated tumor cells triggers the expansion of tumor-specific cytotoxic T lymphocytes (CTL) that reduce the growth of established tumors and prevent their metastatic spread. These findings suggest that CpG-conjugated autologous cancer cells show promise as immunotherapeutic agents and can be effectively combined with surgery to reduce metastasis risk.

• Case 2

Another group focuses on designing a cancer vaccine formulation where the immune adjuvant is loaded into poly (lactic-co-glycolic acid) (PLGA) nanoparticles that are then anchored to the surface of irradiated tumor cells via streptavidin-biotin cross-linking. Promisingly, the hybrid construct comprising cancer cells conjugated to PLGA particles has a significant therapeutic effect as therapeutic cancer vaccines in a prostate tumor model. These engineered cell-particle assemblies have shown a versatility level to the vaccine formulation where the polymeric particles can be loaded with different immune adjuvants or even a combination of immune adjuvants as required.

Fig.1 Cancer cells with adjuvant-loaded PLGA nanoparticles. (Ahmed, 2017)

Cancer Cell Surface Engineering for Targeted Therapy

Distinguishing cancer cells from normal cells through cell-surface receptors, which provide the molecular recognition moieties, is vital for cancer diagnosis and targeted therapy. It can be achieved by engineering and converting some tumor-associated or -specific surface receptors into some detectable reporters.

• Case 3

A research group uses the high metabolic activity of cancer-overexpressed enzymes (histone deacetylase and cathepsin L-responsive acetylated azidomannosamine) to design an enzymatically activatable Ac4ManAz analog, which is subjected to a metabolic labeling process, and further conjugates this analog to glycoproteins highly expressed on the cancer cell surface. Furthermore, they successfully expand the application of this cancer-selective labeling of azide groups for targeted cancer therapy against several selected tumor types via click chemistry. Thus, this strategy may provide a clinical solution and improve in vivo targeting targeted therapy efficiency to challenging diseases lacking targetable antigens.

Fig.2 Active tissue targeting via anchored click chemistry. (Wang, 2017)

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References

1. Shirota, H.; Klinman, D.M. CpG-conjugated apoptotic tumor cells elicit potent tumor-specific immunity. Cancer Immunology, Immunotherapy. 2011, 60(5), pp.659-669.
2. Ahmed, K.K.; et al. Surface engineering tumor cells with adjuvant-loaded particles for use as cancer vaccines. Journal of Controlled Release. 2017, 248, pp.1-9.
3. Wang, H.; et al. Selective in vivo metabolic cell-labeling-mediated cancer targeting. Nature chemical biology. 2017, 13(4), pp.415-424.