2018
DOI: 10.3389/fimmu.2018.02231
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Chimeric Antigen Receptors Based on Low Affinity Mutants of FcεRI Re-direct T Cell Specificity to Cells Expressing Membrane IgE

Abstract: IgE is the key mediator of allergic responses. Omalizumab, an IgE-specific monoclonal antibody that depletes IgE, is effective for treating severe allergic asthma. The need for frequent administration of the expensive drug, however, limits its applications. Taking advantage of T cell memory, adoptive T cell therapy (ACT) targeting IgE-producing cells has the potential to achieve long-term suppression of IgE and relief of symptoms for severe allergic diseases. The transmembrane form of IgE (mIgE), which is pres… Show more

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Cited by 21 publications
(20 citation statements)
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“…These results suggest that B cell depletion with CAR-T cells may provide long term protection in autoimmune diseases. In addition to CD19, the transmembrane IgE receptor expressed on B cells was explored as a B cell target for the CD8 + CAR-T cells ( Table 6 ) ( 242 ).…”
Section: T Cell Therapymentioning
confidence: 99%
“…These results suggest that B cell depletion with CAR-T cells may provide long term protection in autoimmune diseases. In addition to CD19, the transmembrane IgE receptor expressed on B cells was explored as a B cell target for the CD8 + CAR-T cells ( Table 6 ) ( 242 ).…”
Section: T Cell Therapymentioning
confidence: 99%
“…This approach was tested using CAR‐T cells carrying the α chain of the high‐affinity IgE receptor, FCεRI, recognizing the transmembrane form of IgE (mIgE) present only on the B‐cell lineage and using FCεRI α mutants with low affinity to IgE. FCεRIα mutant‐CAR‐Tregs did not activate other cells carrying surface‐bound IgE or trigger degranulation of LAD2 mast cells, while they exerted potent and specific T‐cell responses on mIgE + murine B cells 122 …”
Section: Targeting Severe Phenotypes Of Allergy Asthma and Copd: A mentioning
confidence: 99%
“…Such action may be positive, but also negative, which altogether should be considered when initiating personalized therapy for severe asthmatics and COPD patients 150,151 . As an example of potential positive synergy, CAR‐T cells directed against IgE‐producing B cells 122 may be used in patients with severe asthma where repeated dosing of expensive biologicals, as the anti‐IgE‐specific monoclonal Ab omalizumab, is currently required. The development of BAR‐Tregs, originally designed to suppress B cells producing anti‐factor VIII antibodies, indicate that CAR technology is suitable to target soluble antigens and both T cell‐ and Ab‐mediated responses.…”
Section: Targeting Severe Phenotypes Of Allergy Asthma and Copd: A mentioning
confidence: 99%
“…U ludzi istnieją trzy różne receptory IgE: receptor IgE o niskim powinowactwie -FcεRII (CD23), galektyna 3 o niskim powinowactwie lub białko wiążące epsilon (eBP) oraz receptor o wysokim powinowactwie do IgE -FcεRI [2]. Receptor FcεRI jest obecny na komórkach tucznych, eozynofilach i bazofilach, które odpowiadają za uwalnianie mediatorów stanu zapalnego i degranulację, co powoduje reakcje nadwrażliwości typu I i objawy alergiczne [141]. Wykazano, że celem dla komórek CAR-T mogą być komórki, które wykazują ekspresję IgE, zwłaszcza jego transbłonowej formy (mIgE).…”
Section: Choroby Alergiczne I Astmaunclassified
“…Takimi komórkami są komórki B ośrodka rozmnażania (germinal center B cells -GCB), plazmoblasty, komórki plazmatyczne lub limfocyty pamięci. Na potwierdzenie tej teorii zaprojektowano i przebadano in vitro komórki CAR, zawierające zewnątrzkomórkową domenę łańcucha α FcεRI (FcεRIα) skierowaną przeciwko mIgE [141]. Krążące w płynach biologicznych i tkankach IgE mogą wiązać CAR i blokować ich interakcje z mIgE w tkankach docelowych.…”
Section: Choroby Alergiczne I Astmaunclassified