Abstract 5052
Background
Despite the impressive impact of CTLA4 and PD-1/L1 cancer immunotherapy, a large proportion of patients with many tumor types fail to respond. Lymphocyte activation gene 3 (LAG3) is the third checkpoint receptor that plays an important role in the pathogenesis of cancer. We have previously described a novel methodology in the identification of therapeutic antibodies (US Patent #9810694). Here we report the discovery of first-in-class, naturally occurring LAG3 checkpoint inhibitor in cancer patients.
Methods
Anti-LAG3 antibody presence was evaluated in 35 individuals: 11 healthy donors (controls) and 24 cancer patients in 3 different laboratories blinded to clinical information. Surface plasmon resonance analysis was done using the optical biosensor Biacore T200 where LAG3 protein was covalently immobilized on the optical chip and biosensor signals from human serum samples were analyzed. Western Blotting used recombinant LAG3 loaded on a 10% SDS PAGE followed by blotting with plasma samples followed by biotinylated anti-human Ig and IrDye 800 streptavidin. Plasma anti-LAG3 IP utilized recombinant LAG3 crosslinked to MagResyn Carboxyl beads followed by incubation with plasma, followed by a biotinylated anti-human Ig and IrDye streptavidin. Affinity purification protocol with elution of antigen-specific antibody with pH gradient was developed. REmAb™ Protein Sequencing with WILD™ analysis (Rapid Novor) is performed.
Results
No anti-LAG3 antibodies were detected in the control group. Among three assays there was a complete correlation for presence of anti-LAG3 antibody in 5 patients. Three of these patients had sufficient plasma quantity and anti-LAG3 concentration (21 – 33 µg/ml) to allow for the antibody purification. Immunoglobulin isotypes were IgG and IgM. The ELISA results of purified antibody samples showed a high quantity of LAG3-specific antibody (0.22 mg, 0.52 mg, 0.3 mg in each sample, respectively). The results of the characterization of novel LAG3 checkpoint inhibitor will be presented at the congress.
Conclusions
To our knowledge, this is the first report of checkpoint antibody presence in humans. Further study with cloning and evaluation of therapeutic properties of novel anti-LAG3 antibody in xenograft models will be performed.
Clinical trial identification
Editorial acknowledgement
NA
Legal entity responsible for the study
The authors.
Funding
ILGEN Inc.
Disclosure
I. Tsimafeyeu: Research grant / Funding (self), Shareholder / Stockholder / Stock options, Full / Part-time employment: ILGEN Inc. G. Bratslavsky: Shareholder / Stockholder / Stock options, Officer / Board of Directors: ILGEN Inc.
Resources from the same session
5939 - Matrix metalloproteinases and their tissue inhibitors genes abnormal DNA methylation in breast cancer
Presenter: Olga Simonova
Session: Poster Display session 1
Resources:
Abstract
2703 - Uveal melanoma cell lines depend on multiple signaling pathways for survival
Presenter: John Park
Session: Poster Display session 1
Resources:
Abstract
4849 - XAF1 and ZNF313 complex stimulates ER stress-induced apoptosis via direct GRP78 inhibition.
Presenter: Sungchan Jang
Session: Poster Display session 1
Resources:
Abstract
4801 - XAF1 assembles a destructive complex to induce BRCA1-mediated apoptosis via suppressing ERa and switching estrogen function
Presenter: Seung-hun Jang
Session: Poster Display session 1
Resources:
Abstract
3416 - Cancer associated fibroblasts promote cancer progression via Wnt2 secretion in colorectal cancer
Presenter: Hideaki Karasawa
Session: Poster Display session 1
Resources:
Abstract
4273 - Paired-related homeobox 1 overexpression promotes invasion and metastasis and is a prognostic factor for worse disease-free survival in patients with lung cancer
Presenter: Jung-jyh Hung
Session: Poster Display session 1
Resources:
Abstract
4241 - LncRNA-GC1 contributes to gastric cancer chemo-resistance through inhibition of miR-551b-3p and the overexpression of dysbindin
Presenter: Xin Guo
Session: Poster Display session 1
Resources:
Abstract
5388 - GLPG 1790, a new selective EPHA2 inhibitor, is active in colorectal cancer cell lines belonging to the CMS4/mesenchymal-like subtype
Presenter: Pietro Paolo Vitiello
Session: Poster Display session 1
Resources:
Abstract
5208 - Characterisation of growth hormone signal transduction in primary melanoma cell lines
Presenter: Karla Sousa
Session: Poster Display session 1
Resources:
Abstract
3156 - LAPTM5 protein can regulate TGF-β mediated MAPK and Smad signaling pathways in ovarian cancer cell
Presenter: Yan Gao
Session: Poster Display session 1
Resources:
Abstract