IBoost technology
iBoost or immune-Boost technology is an improved conjugate vaccine technology designed for vaccination against weak or non-immunogenic molecules. This technology is designed to allow vaccination against self-proteins or mutated self-proteins that are specifically and selectively present in tumors, for the treatment of cancer.[1] The application is not limited to cancer and can be applied against pathologies in which disease-specific self-proteins are present. It can also be applied to improve the quality of vaccines against infectious diseases, such as influenza and COVID-19.
Mechanism of action
The iBoost technology is based on the principle of conjugate vaccines. In a conjugate vaccine, the target molecule (e.g. a self-protein) to which an antibody response is aimed, is conjugated to a foreign protein sequence, for example a bacterial protein or peptide. This conjugate is used as the vaccine, often combined with an immune adjuvant. While the foreign sequence gets readily recognized by the immune system, through the conjugation to this foreign sequence the self-protein is also recognized as foreign, and a specific immune response is induced. Mechanistically, after injection of the conjugate vaccine, the immune response against the foreign sequence will generate the production of helper T cells that can support the activation of B cells, resulting in an antibody response against the foreign sequence. Autoreactive B cells specific for the self-protein will take up the conjugate protein and will start antigen presentation, resulting in re-expression of peptides of both self- and foreign sequences in the context of major histocompatibility complex (MHC) class II molecules. These autoreactive B cells get now support from helper T cells that are specific for the foreign sequence. As a result, the autoreactive B cells multiply by cell proliferation and differentiate into plasma cells to produce an efficient antibody response. See the figure. iBoost is an improved conjugate vaccine strategy because the foreign bacterial sequence is engineered to induce a subtle immune response, in favor of the immune response that is induced against the self-protein. iBoost vaccines have to be applied together with a strong immunologic adjuvant.[2]
History
The use of conjugate vaccines was first reported in the 1920s when Oswald Avery conjugated Streptococcus pneumoniae type 3 polysaccharide to bacterial carrier proteins, for use as a vaccine in order to induce an antibody response against these bacteria.[3] As these polysaccharides are weak antigens, so-called T cell independent antigens, the conjugation step was necessary to induce mature antibody responses. The discovery of penicillin by Alexander Fleming in 1928 as an antibiotic against bacterial infection and the commercial use of it in the years after, halted the development of conjugate vaccines. This lasted until conjugate vaccines against polysaccharides became a solution in the 1980s for bacterial infections in babies and young children, as they have an underdeveloped response against T cell independent antigens. Conjugate vaccines for use in cancer patients have been described in the 1990s where tumor growth factors (e.g. epidermal growth factor) conjugated to a carrier protein were used.[4] Several reports on conjugate vaccines have used the tumor vasculature as the vaccination target.[5][6][7][8][9] After the first demonstrations that conjugate vaccination could be a means of vaccination against cancer, iBoost technology was developed and it has shown potential in preclinical studies. iBoost technology was developed in the Angiogenesis Laboratory, which is directed by Arjan W. Griffioen and currently located at Amsterdam UMC in Amsterdam, The Netherlands. The technology was submitted for patent protection by Amsterdam UMC. The patent is currently approved in the US and an exclusive license was given to CimCure BV.
Application for cancer
Since iBoost technology has the potential to induce antibody responses against self-proteins, it can be applied for vaccination against cancer. Development of immunotherapies against cancer has been notoriously difficult as tumors maintain a strong immunosuppressive microenvironment. Mechanisms of immune suppression are numerous, including expression of immunosuppressive cytokines (e.g. interleukin-10 and transforming growth factor beta), propagation of immunosuppressive leukocytes, such as regulatory T cells and myeloid derived suppressor cells, inhibition of cytotoxic T cells, deviation of dendritic cell maturation and endothelial cell anergy. The induction of antibody responses occurs in lymph nodes and spleen and is therefore not hindered by the immune suppression in the tumor. Several studies have shown efficacy of vaccination against cancer in preclinical studies.[10]
Application for infectious diseases
iBoost technology is also applicable for infectious diseases, for example in situations where antibody responses are absent, slow or immature. In COVID-19 it was found that protective antibody responses are rather slow and inefficient. By targeting the immune response towards crucial epitopes in the receptor binding domain (RBD) of the spike protein of SARS-CoV-2, protective vaccination using iBoost was demonstrated.[11]
References
- ↑ Huijbers, Elisabeth J. M.; van Beijnum, Judy R.; Lê, Chung T.; Langman, Sofya; Nowak-Sliwinska, Patrycja; Mayo, Kevin H.; Griffioen, Arjan W. (2018-05-17). "An improved conjugate vaccine technology; induction of antibody responses to the tumor vasculature". Vaccine. 36 (21): 3054–3060. doi:10.1016/j.vaccine.2018.03.064. ISSN 1873-2518. PMID 29655625.
- ↑ van Loon, Karlijn; Huijbers, Elisabeth J. M.; de Haan, Jan David; Griffioen, Arjan W. (2022-05-24). "Cancer Vaccination against Extracellular Vimentin Efficiently Adjuvanted with Montanide ISA 720/CpG". Cancers. 14 (11): 2593. doi:10.3390/cancers14112593. ISSN 2072-6694. PMC 9179438 Check
|pmc=value (help). PMID 35681575 Check|pmid=value (help). - ↑ Avery, Oswald T.; Goebel, Walther F. (1929-10-01). "Chemo-Immunological Studies on Conjugated Carbohydrate-Proteins". Journal of Experimental Medicine. 50 (4): 533–550. doi:10.1084/jem.50.4.533. ISSN 1540-9538. PMC 2131643. PMID 19869645.
- ↑ González, G.; Crombet, T.; Catalá, M.; Mirabal, V.; Hernández, J. C.; González, Y.; Marinello, P.; Guillén, G.; Lage, A. (April 1998). "A novel cancer vaccine composed of human-recombinant epidermal growth factor linked to a carrier protein: report of a pilot clinical trial". Annals of Oncology: Official Journal of the European Society for Medical Oncology. 9 (4): 431–435. doi:10.1023/a:1008261031034. ISSN 0923-7534. PMID 9636835.
- ↑ Huijbers, Elisabeth J. M.; Ringvall, Maria; Femel, Julia; Kalamajski, Sebastian; Lukinius, Agneta; Abrink, Magnus; Hellman, Lars; Olsson, Anna-Karin (November 2010). "Vaccination against the extra domain-B of fibronectin as a novel tumor therapy". FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology. 24 (11): 4535–4544. doi:10.1096/fj.10-163022. ISSN 1530-6860. PMID 20634349. Unknown parameter
|s2cid=ignored (help) - ↑ van Beijnum, Judy R.; Huijbers, Elisabeth J. M.; van Loon, Karlijn; Blanas, Athanasios; Akbari, Parvin; Roos, Arno; Wong, Tse J.; Denisov, Stepan S.; Hackeng, Tilman M.; Jimenez, Connie R.; Nowak-Sliwinska, Patrycja; Griffioen, Arjan W. (2022-05-23). "Extracellular vimentin mimics VEGF and is a target for anti-angiogenic immunotherapy". Nature Communications. 13 (1): 2842. Bibcode:2022NatCo..13.2842V. doi:10.1038/s41467-022-30063-7. ISSN 2041-1723. PMC 9126915 Check
|pmc=value (help). PMID 35606362 Check|pmid=value (help). - ↑ Ferguson, Henry J. M.; Wragg, Joseph W.; Ward, Stephen; Heath, Victoria L.; Ismail, Tariq; Bicknell, Roy (2016-04-12). "Glutamate dependent NMDA receptor 2D is a novel angiogenic tumour endothelial marker in colorectal cancer". Oncotarget. 7 (15): 20440–20454. doi:10.18632/oncotarget.7812. ISSN 1949-2553. PMC 4991466. PMID 26943033.
- ↑ Zhuang, Xiaodong; Ahmed, Forhad; Zhang, Yang; Ferguson, Henry J.; Steele, Jane C.; Steven, Neil M.; Nagy, Zsuzsanna; Heath, Victoria L.; Toellner, Kai-Michael; Bicknell, Roy (January 2015). "Robo4 vaccines induce antibodies that retard tumor growth". Angiogenesis. 18 (1): 83–95. doi:10.1007/s10456-014-9448-z. ISSN 1573-7209. PMID 25348086. Unknown parameter
|s2cid=ignored (help) - ↑ Femel, Julia; van Hooren, Luuk; Herre, Melanie; Cedervall, Jessica; Saupe, Falk; Huijbers, Elisabeth J. M.; Verboogen, Danielle R. J.; Reichel, Matthias; Thijssen, Victor L.; Griffioen, Arjan W.; Hellman, Lars; Dimberg, Anna; Olsson, Anna-Karin (August 2022). "Vaccination against galectin-1 promotes cytotoxic T-cell infiltration in melanoma and reduces tumor burden". Cancer Immunology, Immunotherapy: CII. 71 (8): 2029–2040. doi:10.1007/s00262-021-03139-4. ISSN 1432-0851. PMC 9293851 Check
|pmc=value (help). PMID 35018481 Check|pmid=value (help). - ↑ Huijbers, Elisabeth J. M.; van der Werf, Inge M.; Faber, Lisette D.; Sialino, Lena D.; van der Laan, Pia; Holland, Hanna A.; Cimpean, Anca M.; Thijssen, Victor L. J. L.; van Beijnum, Judy R.; Griffioen, Arjan W. (2019). "Targeting Tumor Vascular CD99 Inhibits Tumor Growth". Frontiers in Immunology. 10: 651. doi:10.3389/fimmu.2019.00651. ISSN 1664-3224. PMC 6455290. PMID 31001265.
- ↑ Blanas, Athanasios; Karsjens, Haiko; de Ligt, Aafke; Huijbers, Elisabeth J. M.; van Loon, Karlijn; Denisov, Stepan S.; Durukan, Canan; Engbersen, Diederik J. M.; Groen, Jan; Hennig, Sven; Hackeng, Tilman M.; van Beijnum, Judy R.; Griffioen, Arjan W. (2022-08-19). "Vaccination with a bacterial peptide conjugated to SARS-CoV-2 receptor-binding domain accelerates immunity and protects against COVID-19". iScience. 25 (8): 104719. Bibcode:2022iSci...25j4719B. doi:10.1016/j.isci.2022.104719. ISSN 2589-0042. PMC 9252865 Check
|pmc=value (help). PMID 35813877 Check|pmid=value (help).
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