Enhanced Cell Therapy

Cell therapy has attracted increasing attention in providing treatments for tissue degeneration, chronic inflammation, autoimmunity, genetic disorders, infections and cancers. Because the efficacy of cell therapy heavily depends on manipulating the fate and function of therapeutic cells, innovative strategies are continuously being introduced to enhance cell survival, boost native behaviors, add new functions, and improve therapeutic effects. By tailoring new characteristics and functions to cells, cell surface engineering has been a very promising approach to enhance novel cell-based therapeutics.

Cell Therapy and Cell Surface Engineering

Cell therapy has provided new and unique strategies to address many unmet medical needs, including genetic engineering, disease treatment, drug delivery, regenerative medicine as well as bioimaging. To improve the therapeutic efficiency, genetic and non-genetic engineering strategies have been developed to meet different demands. Although genetic modification is a powerful tool, it has a number of significant drawbacks, such as (1) the safety issue of gene delivery viral vector; (2) time-consuming process; (3) permanent and irreversible problem; (4) not applicable to all types of cells. Complementarily, cell surface engineering usually involving non-genetic engineering strategy, has emerged as a powerful and compatible complement to enhance the function of cells and cell-based therapeutics.

Fig.1 Engineering the surface of therapeutic “living” cells. (Park, 2018)

Cell Surface Engineering to Enhance Cell Therapy

In recent years, a wide range of new molecules, artificial receptors, and multifunctional nanomaterials have been introduced to the surface of therapeutic cells, synthetically endowing donor cells with new properties and functions.

• Case 1

Frank, et al. conjugated monoclonal antibodies including rituximab and daratumumab to the cell surface proteins to study the effects of cellular therapy. They found that the antitumor activity of γδ T cells, NK cells, and cytokine-induced killer (CIK) cells can be augmented by rapidly affixing tumor-targeting antibodies directly to cell surface proteins. This cell surface conjugation is flexible and simple without the need for genetic engineering.

• Case 2

To address the challenge of rapid decline in viability and function of the transplanted cells, Stephan, et al. described a strategy to enhance cell therapy via the conjugation of adjuvant drug loaded nanoparticles to the surfaces of T cells and HSCs via cell-surface thiols. Through this surface-conjugation, they observed marked enhancements in tumor elimination in a model of adoptive T cell therapy for cancer. Moreover, this approach is a simple and generalizable strategy to augment cytoreagents while minimizing the systemic side effects of adjuvant drugs.

• Case 3

Surface engineering of tumor cells with a variety of immune modifiers and costimulatory agents has been leveraged for both therapeutic and diagnostic purposes, especially enhancing the immune recognition and responsiveness of the tumor cell vaccines. Shirota, et al. covalently conjugated immunostimulatory oligodeoxynucleotides containing unmethylated cytosine guanosine (CpG) dinucleotides (CpG OND) to apoptotic tumor cells via an amine-to-amine cross-linker. They revealed that CpG OND conjugation enhanced the uptake of tumor-associated antigens (TAAs) by dendritic cells, induced costimulatory molecule expression, and promoted the production of antitumor cytokines.

Cell surface engineering offers a powerful complement to traditional genetic engineering strategies for enhancing the therapeutic function of living cells. With a forward-looking insight and intuition, Creative Biolabs has been equipped with advanced instruments, fit-for-purpose laboratories, and professional scientists to provide flexible solutions for cell surface engineering. We can provide various conjugates for your choice, either stand-alone service or integrated project is both welcome to meet every specific demand.

If you are interested in our services, please feel free to contact us.

References

1. Park, J.; et al. Engineering the surface of therapeutic “living” cells. Chemical reviews. 2018, 118(4): 1664-1690.
2. Frank, M. J.; et al. A Novel Antibody-Cell Conjugation Method to Enhance Cellular Therapies for the Treatment of Hematological Malignancies. Blood. 2017, 130(Supplement 1): 1532-1532.
3. Stephan, M. T.; et al. Therapeutic cell engineering with surface-conjugated synthetic nanoparticles. Nature medicine. 2010, 16(9): 1035-1041.
4. Shirota, H.; Klinman, D. M. CpG-conjugated apoptotic tumor cells elicit potent tumor-specific immunity. Cancer Immunology. Immunotherapy. 2011, 60(5): 659-669.