| 000 | 04209nlm1a2200493 4500 | ||
|---|---|---|---|
| 001 | 664015 | ||
| 005 | 20231030041915.0 | ||
| 035 | _a(RuTPU)RU\TPU\network\35185 | ||
| 035 | _aRU\TPU\network\35184 | ||
| 090 | _a664015 | ||
| 100 | _a20210323a2020 k y0engy50 ba | ||
| 101 | 0 | _aeng | |
| 135 | _adrcn ---uucaa | ||
| 181 | 0 | _ai | |
| 182 | 0 | _ab | |
| 200 | 1 |
_aEvaluating the Therapeutic Efficacy of Mono- and Bivalent Affibody-Based Fusion Proteins Targeting HER3 in a Pancreatic Cancer Xenograft Model _fCh. D. Leitao, S. S. Rinne, M. Altai [et al.] |
|
| 203 |
_aText _celectronic |
||
| 300 | _aTitle screen | ||
| 320 | _a[References: 29 tit.] | ||
| 330 | _aHuman epidermal growth factor receptor 3 (HER3) has been increasingly scrutinized as a potential drug target since the elucidation of its role in mediating tumor growth and acquired therapy resistance. Affibody molecules are so-called scaffold proteins with favorable biophysical properties, such as a small size for improved tissue penetration and extravasation, thermal and chemical stability, and a high tolerance to modifications. Additionally, affibody molecules are efficiently produced in prokaryotic hosts or by chemical peptide synthesis. We have previously evaluated the biodistribution profiles of five mono- and bivalent anti-HER3 affibody molecules (designated as 3) fused to an albumin-binding domain (designated as A), 3A, 33A, 3A3, A33, and A3, that inhibit ligand-dependent phosphorylation. In the present study, we examined the therapeutic efficacy of the three most promising variants, 3A, 33A, and 3A3, in a direct comparison with the HER3-targeting monoclonal antibody seribantumab (MM-121) in a preclinical BxPC-3 pancreatic cancer model. Xenografted mice were treated with either an affibody construct or MM-121 and the tumor growth was compared to a vehicle group. Receptor occupancy was estimated by positron emission tomography/computed tomography (PET/CT) imaging using a HER3-targeting affibody imaging agent [68Ga]Ga-(HE)3-Z08698-NODAGA. The affibody molecules could inhibit ligand-dependent phosphorylation and cell proliferation in vitro and demonstrated tumor growth inhibition in vivo comparable to that of MM-121. PET/CT imaging showed full receptor occupancy for all tested drug candidates. Treatment with 3A and 3A3 affibody constructs was more efficient than with 33A and similar to the anti-HER3 antibody seribantumab, showing that the molecular design of affibody-based therapeutics targeting HER3 in terms of the relative position of functional domains and valency has an impact on therapeutic effect. | ||
| 461 | _tPharmaceutics | ||
| 463 |
_tVol. 12, iss. 6 _v[551, 15 p.] _d2020 |
||
| 610 | 1 | _aэлектронный ресурс | |
| 610 | 1 | _aтруды учёных ТПУ | |
| 610 | 1 | _aaffibody molecules | |
| 610 | 1 | _aHER3 | |
| 610 | 1 | _aalbumin-binding domain | |
| 610 | 1 | _aseribantumab | |
| 610 | 1 | _atherapy | |
| 610 | 1 | _aMM-121 | |
| 701 | 1 |
_aLeitao _bCh. D. _gCharles Dahlsson |
|
| 701 | 1 |
_aRinne _bS. S. _gSara |
|
| 701 | 1 |
_aAltai _bM. _gMohamed |
|
| 701 | 1 |
_aVorontsova _bO. _gOlga |
|
| 701 | 1 |
_aDunas _bF. _gFinn |
|
| 701 | 1 |
_aJonasson _bP. _gPer |
|
| 701 | 1 |
_aTolmachev _bV. M. _cspecialist in the field of medical technology _cDirector of the Research Center "Oncoteranostika", Tomsk Polytechnic University, Ph.D _f1961- _gVladimir Maksimilianovich _2stltpush _3(RuTPU)RU\TPU\pers\46552 |
|
| 701 | 1 |
_aLofblom _bJ. _gJohn |
|
| 701 | 1 |
_aStahl _bS. _gStefan |
|
| 701 | 1 |
_aOrlova _bA. M. _cspecialist in the field of medical technology _cSenior Researcher, Oncoteranostika Research Center, Tomsk Polytechnic University, Ph.D _f1960- _gAnna Markovna _2stltpush _3(RuTPU)RU\TPU\pers\46554 |
|
| 712 | 0 | 2 |
_aНациональный исследовательский Томский политехнический университет _bИсследовательская школа химических и биомедицинских технологий _bНаучно-исследовательский центр "Онкотераностика" _h8442 _2stltpush _3(RuTPU)RU\TPU\col\27561 |
| 801 | 2 |
_aRU _b63413507 _c20210323 _gRCR |
|
| 856 | 4 | _uhttps://doi.org/10.3390/pharmaceutics12060551 | |
| 942 | _cCF | ||