An oligo-His-tag of a targeting module does not influence its biodistribution and the retargeting capabilities of UniCAR T cells
| Autor: | Jureczek, J., Bergmann, R., Berndt, N., Koristka, S., Kegler, A., Puentes-Cala, E., Soto, J. A., Arndt, C., Bachmann, M., Feldmann, A. |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Cytotoxicity
Immunologic Male T-Lymphocytes Mice Nude lcsh:Medicine Cancer immunotherapy GPI-Linked Proteins Immunotherapy Adoptive Article Mice Antigens Neoplasm Animals Humans Tissue Distribution lcsh:Science Sequence Tagged Sites Receptors Chimeric Antigen lcsh:R Prostatic Neoplasms Xenograft Model Antitumor Assays Neoplasm Proteins Positron-Emission Tomography PC-3 Cells Cytokines lcsh:Q Oligopeptides |
| Zdroj: | Repositorio Universidad de Santander Universidad de Santander instacron:Universidad de Santander Scientific Reports, Vol 9, Iss 1, Pp 1-15 (2019) Scientific Reports Scientific Reports 9(2019)1, 10547 |
| Popis: | Digital Recently, we established the controllable modular UniCAR platform technology to advance the efficacy and safety of CAR T cell therapy. The UniCAR system is composed of (i) target modules (TMs) and (ii) UniCAR armed T cells. TMs are bispecific molecules that are able to bind to the tumor cell surface and simultaneously to UniCAR T cells. For interaction with UniCAR T cells, TMs contain a peptide epitope sequence which is recognised by UniCAR T cells. So far, a series of TMs against a variety of tumor targets including against the prostate stem cell antigen (PSCA) were constructed and functionally characterised. In order to facilitate their purification all these TMs are expressed as recombinant proteins equipped with an oligo-His-tag. The aim of the here presented manuscript was to learn whether or not the oligo-His-tag of the TM influences the UniCAR system. For this purpose, we constructed TMs against PSCA equipped with or lacking an oligo-His-tag. Both TMs were compared side by side including for functionality and biodistribution. According to our data, an oligo-His-tag of a UniCAR TM has only little if any effect on its binding affinity, in vitro and in vivo killing capability and in vivo biodistribution. 1 ed. |
| Databáze: | OpenAIRE |
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