An Fc-muted bispecific antibody targeting PD-L1 and 4-1BB induces antitumor immune activity in colorectal cancer without systemic toxicity.

Background: Resistance to immune checkpoint inhibitor (ICI) therapy narrows the efficacy of cancer immunotherapy. Although 4-1BB is a promising drug target as a costimulatory molecule of immune cells, no 4-1BB agonist has been given clinical approval because of severe liver toxicity or limited efficacy. Therefore, a safe and efficient immunostimulatory molecule is urgently needed for cancer immunotherapy.

A humanized 4-1BB-targeting agonistic antibody exerts potent antitumor activity in colorectal cancer without systemic toxicity.

Background: Colorectal cancer (CRC) is one of the most common malignancies and the patient survival rate remains unacceptably low. The anti-programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibody-based immune checkpoint inhibitors have been added to CRC treatment regimens, however, only a fraction of patients benefits. As an important co-stimulatory molecule, 4-1BB/CD137 is mainly expressed on the surface of immune cells including T and natural killer (NK) cells.

[Preparation and identification of monoclonal antibodies against snake venom C-type lectin like protein Agkisacutacin].

Aim: To prepare and identify the antibodies against snake venom C-type lectin like protein Agkisacutacin.

Methods: A BALB/c mouse was immunized with Agkisacutacin and the cells were fused by standard hybridoma technique to prepare mAbs. The stability of the hybridomas secreting mAbs was detected by indirect ELISA.

[Downregulation of HER2 by adenovirus-mediated RNA interference and its inhibitory effect on growth of SKBR3 breast cancer cell].

Aim: To explore the possibility of RNA interference (RNAi)-based gene therapy against HER2-overexpressing tumors using adenovirus-mediated vector.

Methods: A plasmid named pHER2-GFP containing HER2 and green fluorescent protein (GFP) fusion was constructed and cotransfected into CHO-K1 cells respectively with nine small interference RNA (siRNA)-expressing plasmids targeting different regions of HER2. The siRNA-expressing plasmids with best interference effect were screened out and then used to identify the gene silence effect in HER2-overexpressing SKBR3 breast cancer cells.

[Apoptotic effect of the combined treatment of engineered antibody with paclitaxel on BT474 cells].

Aim: To explore the apoptotic effect of the combined treatment of anti-p185(c-erbB-2/neu) engineered antibody with paclitaxel on p185-overexpressing human malignant breast cancer cell lines BT474 and to study its emerging mechanism.

Methods: The prohibitory effect of engineeded antibody plus paclitaxel on BT474 cells was assessed by MTS assay. The number of apoptotic cells was detected by Annexin V-FITC/PI.

[Effects of anti-HER-2 chimeric antibody chA21 on proliferative inhibition of SKOV3 cells and inducing their apoptosis].

Aim: To explore the effects of anti-HER-2 chimeric antibody chA21 on proliferation and apoptosis of ovarian cancer cell lines SKOV3.

Methods: MTT colorometric assay, HE staining, transmission electron microscopy, flow cytometry and TUNEL staining were used to study the proliferative inhibition and apoptotic induction of SKOV3 cells by chA21 in vitro.

Results: Proliferative inhibition rate and apoptotic rate of SKOV3 cells were increased with dose and action time by chA21 (0.

[Soluble expression and characterization of disulfide bond-rich subdomains of membrane protein p185 in Escherichia coli].

Transmembrane protein p185 (the product of Her2/c-erbB-2 gene) is a member of the epidermal growth factor receptor (EGFR) family. Its overexpression was found in about 30% of breast cancer. It is essential to obtain soluble extracellular domain (ECD) of p185, especially disulfide bond rich domains, for identifying the epitopes of anti-p185 antibodies and researching the interrelationship between the antigen and antibody.

[Metabolism of 125I labeled anti-p185 antibodies in vitro and their biodistribution in vivo].

Aim: To study the cellular metabolism(RIA) in vitro and the biodistribution in vivo of (125)I labeled anti-p185 antibodies(murine mAb A21, mouse-human chimeric antibody A21scFv-Fc and single chain antibody A21 scFv), to provide the basis for clinical application in the diagnosis and treatment of tumor overexpressing p185.

Methods: The specificity of binding of these antibodies to SKOV(3) known to highly express surface antigen p185 was assessd by FACS. The metabolism of the antibodies in SKOV(3) was assayed by cellular RIA.

Construction, expression and characterization of the engineered antibody against tumor surface antigen, p185(c-erbB-2).

The c-erbB-2 proto-oncogene encodes a 185kDa protein p185, which belongs to epidermal growth factor receptor family. Amplification of this gene has been shown to correlate with poor clinical prognosis for certain cancer patients. The monoclonal antibody A21 which directed against p185 specifically inhibits proliferation of tumor cells overexpressing p185, hence allows it to be a candidate for targeted therapy.