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Co-culture platform...
Co-culture platform for tuning of cancer receptor density allows for evaluation of bispecific immune cell engagers
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- Mebrahtu, Aman (författare)
- KTH,Proteinteknologi
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- Aniander, Gustav (författare)
- KTH,Proteinteknologi
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- Mega, Alessandro (författare)
- Affibody Medical AB, Scheeles väg 2, SE-171 65 Solna, Sweden, Scheeles väg 2
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- Moradi, Mona (författare)
- KTH,Proteinteknologi
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- Thalén, Niklas (författare)
- KTH,Proteinteknologi
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- Gudmundsdotter, Lindvi (författare)
- Affibody Medical AB, Scheeles väg 2, SE-171 65 Solna, Sweden, Scheeles väg 2
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- Backström Rydin, Eva (författare)
- Affibody Medical AB, Scheeles väg 2, SE-171 65 Solna, Sweden, Scheeles väg 2
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- Sandegren, Anna (författare)
- Affibody Medical AB, Scheeles väg 2, SE-171 65 Solna, Sweden, Scheeles väg 2
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- Frejd, Fredrik Y. (författare)
- Affibody Medical AB, Scheeles väg 2, SE-171 65 Solna, Sweden, Scheeles väg 2
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- Rockberg, Johan (författare)
- KTH,Proteinteknologi
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(creator_code:org_t)
- Elsevier BV, 2024
- 2024
- Engelska.
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Ingår i: New Biotechnology. - : Elsevier BV. - 1871-6784 .- 1876-4347. ; 79, s. 120-126
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Cancer immunotherapy, where a patient's immune system is harnessed to eradicate cancer cells selectively, is a leading strategy for cancer treatment. However, successes with immune checkpoint inhibitors (ICI) are hampered by reported systemic and organ-specific toxicities and by two-thirds of the patients being non-responders or subsequently acquiring resistance to approved ICIs. Hence substantial efforts are invested in discovering novel targeted immunotherapies aimed at reduced side-effects and improved potency. One way is utilizing the dual targeting feature of bispecific antibodies, which have made them increasingly popular for cancer immunotherapy. Easy and predictive screening methods for activation ranking of candidate drugs in tumor contra non-tumor environments are however lacking. Herein, we present a cell-based assay mimicking the tumor microenvironment by co-culturing B cells with engineered human embryonic kidney 293 T cells (HEK293T), presenting a controllable density of platelet-derived growth factor receptor β (PDGFRβ). A target density panel with three different surface protein levels on HEK293T cells was established by genetic constructs carrying regulatory elements limiting RNA translation of PDGFRβ. We employed a bispecific antibody-affibody construct called an AffiMab capable of binding PDGFRβ on cancer cells and CD40 expressed by B cells as a model. Specific activation of CD40-mediated signaling of immune cells was demonstrated with the two highest receptor-expressing cell lines, Level 2/3 and Level 4, while low-to-none in the low-expressing cell lines. The concept of receptor tuning and the presented co-culture protocol may be of general utility for assessing and developing novel bi-specific antibodies for immuno-oncology applications.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- Expression tuning
- Receptor density
- Regulatory elements
- Screening platform
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Mebrahtu, Aman
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Aniander, Gustav
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Mega, Alessandro
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Moradi, Mona
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Thalén, Niklas
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Gudmundsdotter, ...
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visa fler...
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Backström Rydin, ...
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Sandegren, Anna
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Frejd, Fredrik Y ...
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Rockberg, Johan
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Immunologi inom ...
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