Combined treatment with netrin-1 interfering drug and immune checkpoint inhibitor drugs
An immune checkpoint and inhibitor technology, applied in drug combinations, immunoglobulins, anti-growth factor immunoglobulins, etc., can solve problems such as unclear cellular immunogenicity
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Embodiment 1
[0148] Materials and methods
[0149] cell line:
[0150] mouse breast cancer EMT6 ( CRL2755 TM - LGC standard - France) cells were cultured in Eagle's minimum essential medium supplemented with 10% fetal bovine serum and antibiotics (streptomycin and penicillin).
[0151] Mus musculus (Mus Musculus) mammary gland 4T1 ( CRL2539 TM - LGC Standard - France) cells were cultured in Dulbecco's Modified Eagle's Medium (DMEM), 10% FBS.
[0152] Mouse experiments:
[0153] Mice were maintained in a specific pathogen-free animal facility and handled according to institutional guidelines and protocols approved by the Animal Care and Use Committee (Leon Berard Center Joint Evaluation Committee, ENS Transit Animals, PBES and P4 Laboratories; CECCAP ).
[0154] Will 5.10 5 or 10.10 5EMT6 cells were transplanted subcutaneously into the flanks of BalbC / J 8-week-old female mice. On days 7, 11 and 14, all animals were treated 3 times with 400 μg / injection of anti-CTLA4 (BioX ...
Embodiment 2
[0170] Will 5.10 5 E0771 cells were transplanted subcutaneously into the flank of C57b6J 8-week-old female mice. Six days after transplantation, animals were randomly divided into 4 groups and treated with NP137 or NP001 IgG1 control isotypes alone or in combination with anti-PD-1 antibody. All animals were treated twice weekly with 20 mg / Kg of anti-CTLA4 (BioX cells-clone 9H10) and / or 10 mg / Kg of NP antibody by IP route. Tumor volumes were measured twice a week by external calipers. When the tumor reaches 2000mm 3 When the volume was reached, the mice were sacrificed.
[0171] Will 5.10 5 MC38 cells were transplanted subcutaneously into the flank of C57b6J 8-week-old female mice. Six days after transplantation, animals were randomly divided into 4 groups and treated with NP137 or NP001 IgG1 control isotypes alone or in combination with anti-PD-1 antibody. All animals were treated twice weekly with 5 mg / Kg of anti-PD1 (BioX cell-clone RMP1-14) and / or 10 mg / Kg of NP antib...
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