Development of novel monoclonal antibodies to dog leukocyte antigen DR displaying direct and immune‐mediated cytotoxicity toward canine lymphoma cell lines
PBN-AR
Instytucja
Wydział Medycyny Weterynaryjnej (Uniwersytet Przyrodniczy we Wrocławiu)
Informacje podstawowe
Główny język publikacji
angielski
Czasopismo
Hematological Oncology (25pkt w roku publikacji)
ISSN
0278-0232
EISSN
1099-1069
Wydawca
WILEY-BLACKWELL
DOI
URL
Rok publikacji
2018
Numer zeszytu
3
Strony od-do
554-560
Numer tomu
36
Identyfikator DOI
Liczba arkuszy
0.5
Autorzy
Pozostali autorzy
+ 4
Autorzy przekładu
(liczba autorów przekładu: 0)
Słowa kluczowe
angielski
canine lymphoma
direct cytotoxicity
DLA‐DR
monoclonal antibodies
Streszczenia
Język
angielski
Treść
Spontaneous canine lymphoma (CL) has become a promising, nonrodent model for advancing the therapeutic strategies of human hematological malignancies. As new resources for veterinary and comparative studies on CL‐associated antigens, we developed 2 novel mouse monoclonal antibodies, denoted B5 and E11, that recognized the canine major histocompatibility Class II DR antigens (dog leukocyte antigen DR). Using flow cytometry and solid phase immunoenzymatic assays, we showed that the antigens recognized by B5 and E11 were strongly expressed in several CL cell lines and the ex vivo canine neoplastic cells of B and mixed B/T immunophenotypes. Additionally, we evaluated a minimal cross‐reactivity of B5 and E11 with the human B‐cell line, Raji. By the ectopic expression of the hybrid murine/canine I‐E/DR dimers in the HEK293 cells, we demonstrated that the epitope of B5 was localized to the invariant DRα chain, whereas the epitope of E11 was collectively formed by the DRα and DRβ chains. Both epitopes were conformational and conserved in all the tested unrelated individuals of different dog breeds. In vitro treatment of 2 CL B‐cell lines (CLBL1 and CLB70) with B5 and E11 rapidly induced a direct apoptotic cell death. Similarily, both mouse monoclonal antibodies efficiently killed the above cell lines through the mechanisms of complement‐dependent and antibody‐mediated cellular phagocytosis. Collectively, our data support the further development of B5 and E11 as novel tools for dog leukocyte antigen DR‐targeted, preclinical trials involving CL.
Inne
System-identifier
UPWr63a0e329eea94d6eaba0cd60be78040a
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