From Lab to Clinic: The Production of Different Types of Recombinant Antibodies as Cancer Treatments
DOI:
https://doi.org/10.47611/jsrhs.v13i4.8317Keywords:
Recombinant Antibodies, Monoclonal Antibodies, Antibodies, Recombinant Technology, Single Chain Variable Fragment, Fragment Antigen Binding, Bispecific, ScFv, Fab, BsAb, Production, Cancer Treatment, ImmunotherapyAbstract
Cancer is one of the leading causes of death worldwide, with a wide variety of treatments targeting it but no definite cure. Within the category of immunotherapy, which is focused on using one’s own immune system to target tumors, is monoclonal antibodies (mAbs). The expanding treatment of recombinant monoclonal antibodies made using recombinant DNA technology has proven that it provides several benefits over the traditional monoclonal antibodies made with hybridoma technology. There are multiple formats of recombinant antibodies defined by their structure, of which the most common are single chain variable fragment (scFv), fragment antigen binding (Fab), and bispecific (bsAb). Using literature review, this paper intends to evaluate and compare the production and structures of recombinant scFv, Fab, and bsAb antibodies, with minimal mention of the application of each. It is found that the production methods for each format are very similar, though bispecific antibodies differ the most due to their structure. There are also differences in the methods used to ensure soluble expression of antibodies in each format. New recombinant antibodies are still being developed with the goal of minimizing production time and labor while maximizing stability and specificity. This paper will help in future research dedicated to production methods that would minimize the cost of recombinant antibody therapy for cancer patients in the future.
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Ahmad, Z. A., Yeap, S. K., Ali, A. M., Ho, W. Y., Alitheen, N. B., & Hamid, M. (2012). scFv antibody: principles and clinical application. Journal of Immunology Research, 130(2), 722–726. https://doi.org/10.1155/2012/980250
Alexander E. Karu, Christopher W. Bell, Tina E. Chin, (1995). Recombinant Antibody Technology, ILAR Journal, 37(3), 132–141https://doi.org/10.1093/ilar.37.3.132
Alfaleh, M. A., Alsaab, H. O., Mahmoud, A. B., Alkayyal, A. A., Jones, M. L., Mahler, S. M., & Hashem, A. M. (2020). Phage Display Derived Monoclonal Antibodies: From Bench to Bedside. Frontiers in immunology, 11, 1896-. https://doi.org/10.3389/fimmu.2020.01986
Allen HC, Sharma P. Histology, Plasma Cells. [Updated 2022 Dec 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan- https://www.ncbi.nlm.nih.gov/books/NBK556082/
Azenta Life sciences. (2022). Monoclonal Antibody Production: Hybridoma vs. Recombinant. https://www.azenta.com/blog/monoclonal-antibody-production-hybridoma-vs-recombinant
Barzaman, K., Moradi-Kalbolandi, S., Hosseinzadeh, A., Kazemi, M. H., Khorramdelazad, H., Safari, E., & Farahmand, L. (2021). Breast cancer immunotherapy: Current and novel approaches. International immunopharmacology, 98, 107886. https://doi.org/10.1016/j.intimp.2021.107886
Bashir, S., & Paeshuyse, J. (2020). Construction of Antibody Phage Libraries and Their Application in Veterinary Immunovirology. Antibodies (Basel, Switzerland), 9(2), 21. https://doi.org/10.3390/antib9020021
Basu, K., Green, E. M., Cheng, Y., & Craik, C. S. (2019). Why recombinant antibodies - benefits and applications. Current opinion in biotechnology, 60, 153–158. https://doi.org/10.1016/j.copbio.2019.01.012
Medline Plus. (n.d.). Bevacizumab Injection. https://medlineplus.gov/druginfo/meds/a607001.html
Britannica, T. Editors of Encyclopaedia (2024, July 30). Molecule. Encyclopedia Britannica. https://www.britannica.com/science/molecule
Cancer Research UK (2021). Checkpoint inhibitors. https://www.cancerresearchuk.org/about-cancer/treatment/immunotherapy/types/checkpoint-inhibitors
Carvalho, L. S., Silva, O. B. da, Almeida, G. C. da, Oliveira, J. D. de, Parachin, N. S., & Carmo, T. S. (2017). Production Processes for Monoclonal Antibodies. InTech. https://doi.org/10.5772/64263
Carter D, (2021). T cells, B cells and the immune system.MD Anderson Cancer Center. https://www.mdanderson.org/cancerwise/t-cells--b-cells-and-the-immune-system.h00-159465579.htm
Cleveland Clinic (2022). Immunotherapy. https://my.clevelandclinic.org/health/treatments/11582-immunotherapy
DeLuca, K. F., Mick, J. E., & DeLuca, J. G. (2022). Production and purification of recombinant monoclonal antibodies from human cells based on a primary sequence. STAR protocols, 3(4), 101915. https://doi.org/10.1016/j.xpro.2022.101915
Dobosz, P., & Dzieciątkowski, T. (2019). The Intriguing History of Cancer Immunotherapy. Frontiers in immunology, 10, 2965. https://doi.org/10.3389/fimmu.2019.02965
Harding, F. A., Stickler, M. M., Razo, J., & DuBridge, R. B. (2010). The immunogenicity of humanized and fully human antibodies: residual immunogenicity resides in the CDR regions. mAbs, 2(3), 256–265. https://doi.org/10.4161/mabs.2.3.11641
Huehls, A. M., Coupet, T. A., & Sentman, C. L. (2015). Bispecific T-cell engagers for cancer immunotherapy. Immunology and cell biology, 93(3), 290–296. https://doi.org/10.1038/icb.2014.93
International Agency of Research in Cancer (n.d.). Cancer today. Incidence in both sexes, in 2022. https://gco.iarc.fr/today/en/dataviz/tables?mode=cancer&group_populations=1&multiple_populations=1&types=0
Kaunitz J. D. (2017). Development of Monoclonal Antibodies: The Dawn of mAb Rule. Digestive diseases and sciences, 62(4), 831–832. https://doi.org/10.1007/s10620-017-4478-1
Kennel, S. J., Flynn, K., Foote, L., & Lankford, T. (1984). Monoclonal Antibodies in Cancer Detection and Therapy. BioScience, 34(3), 150–156. https://doi.org/10.2307/1309749
Klein, C., Brinkmann, U., Reichert, J. M., & Kontermann, R. E. (2024). The present and future of bispecific antibodies for cancer therapy. Nature reviews. Drug discovery, 23(4), 301–319. https://doi.org/10.1038/s41573-024-00896-6
Kochanek, K. D., Murphy, S. L., Xu, J. Q., Arias, E. (2023, December). Mortality in the United States, 2022 (NCHS Data Brief, No. 492). Hyattsville, MD: National Center for Health Statistics. https://dx.doi.org/10.15620/cdc:135850
Kontermann, R. E., (2005). Recombinant bispecific antibodies for cancer therapy. Acta Pharmacologica Sinica, 26(1), 1-9. https://doi.org/10.1111/j.1745-7254.2005.00008.x
Lee, K. W., Yam, J. W. P., & Mao, X. (2023). Dendritic Cell Vaccines: A Shift from Conventional Approach to New Generations. Cells, 12(17), 2147. https://doi.org/10.3390/cells12172147
Müller, V., Clemens, M., Jassem, J., Al-Sakaff, N., Auclair, P., Nüesch, E., Holloway, D., Shing, M., & Bang, Y. J. (2018). Long-term trastuzumab (Herceptin®) treatment in a continuation study of patients with HER2-positive breast cancer or HER2-positive gastric cancer. BMC cancer, 18, Article 295. https://doi.org/10.1186/s12885-018-4183-2
National Center for Health Statistics. (2024) Leading Causes of Death. https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm
Paduano, F. ( n.d). Recombinant Antibodies https://www.antibodies.com/primary-antibodies/recombinant-antibodies
Pardoll D. M. (2012). The blockade of immune checkpoints in cancer immunotherapy. Nature reviews. Cancer, 12(4), 252–264. https://doi.org/10.1038/nrc3239
Pirkalkhoran, S., Grabowska, W. R., Kashkoli, H. H., Mirhassani, R., Guiliano, D., Dolphin, C., & Khalili, H. (2023). Bioengineering of Antibody Fragments: Challenges and Opportunities. Bioengineering (Basel, Switzerland), 10(2), 122. https://doi.org/10.3390/bioengineering10020122
Roche. (n.d). Avastin (bevacizumab). Roche. Retrieved August 10, 2024, from https://www.roche.com/solutions/pharma/productid-d263d2d3-708f-4fbd-87da-23364b2958f6
Roser, M. (2021). Causes of death globally: what do people die from? www.OurWorldInData.org
Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49. https://doi.org/10.3322/caac.21820
Thermofisher Scientific (n.a.). Monoclonal vs. Polyclonal Antibodies. https://www.thermofisher.com/us/en/home/life-science/antibodies/primary-antibodies/monoclonal-vs-polyclonal-antibodies.html
Tiller T. (2011). Single B cell antibody technologies. New biotechnology, 28(5), 453–457. https://doi.org/10.1016/j.nbt.2011.03.014
What is Biotechnology (n.d.) Making monoclonal antibodies https://www.whatisbiotechnology.org/index.php/exhibitions/milstein/monoclonals
Wu, X., Sereno, A. J., Huang, F., Lewis, S. M., Lieu, R. L., Weldon, C., Torres, C., Fine, C., Batt, M. A., Fitchett, J. R., Glasebrook, A. L., Kuhlman, B., & Demarest, S. J. (2015). Fab-based bispecific antibody formats with robust biophysical properties and biological activity. mAbs, 7(3), 470–482. https://doi.org/10.1080/19420862.2015.1022694
Xie, X., Zhang, J., Wang, Y., Shi, W., Tang, R., Tang, Q., Sun, S., Wu, R., Xu, S., Wang, M., Liang, X., & Cui, L. (2023). Nanomaterials augmented bioeffects of ultrasound in cancer immunotherapy. Materials today. Bio, 24, 100926. https://doi.org/10.1016/j.mtbio.2023.100926
Zider, A., & Drakeman, D. L. (2010). The future of monoclonal antibody technology. mAbs, 2(4), 361–364. https://doi.org/10.4161/mabs.12461
Zheng, K., Bantog, C., & Bayer, R. (2011). The impact of glycosylation on monoclonal antibody conformation and stability. mAbs, 3(6), 568–576. https://doi.org/10.4161/mabs.3.6.17922
Zwolak, A., Leettola, C. N., Tam, S. H., Goulet, D. R., Derebe, M. G., Pardinas, J. R., Zheng, S., Decker, R., Emmell, E., & Chiu, M. L. (2017). Rapid Purification of Human Bispecific Antibodies via Selective Modulation of Protein A Binding. Scientific reports, 7(1), 15521. https://doi.org/10.1038/s41598-017-15748-0
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Copyright (c) 2024 Dishetha Mamidi; Prahlad Parajuli, Virgel Torremocha, Jothsna Kethar
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