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
1613 - Lerociclib (G1T38), an oral CDK4/6 inhibitor, dosed continuously in combination with osimertinib for EGFRmut non-small cell lung cancer: initial Phase 1b results
Presenter: David Berz
Session: Poster Display session 1
Resources:
Abstract
2853 - Real-world implementation of sequential targeted therapies for EGFR-mutated NSCLC
Presenter: Petros Christopoulos
Session: Poster Display session 1
Resources:
Abstract
1974 - A Phase II Open-Label, Multicentre Study to Assess the Anti-tumour Activity of Afatinib in Patients with Activating Epidermal Growth Factor Receptor mutation (EGFRm) from Circulating Tumor DNA (CtDNA)
Presenter: Young-Chul Kim
Session: Poster Display session 1
Resources:
Abstract
3370 - Influence of cow’s milk on the absorption and exposure of erlotinib in NSCLC patients
Presenter: Geerten Veerman
Session: Poster Display session 1
Resources:
Abstract
5900 - PTEN loss as Predictor of Tumor Heterogeneity (TH) and Poor Prognosis in EGFR-mutant Advanced Non-Small Cell Lung Cancer (ANSCLC) Patients (pts) Receiving Tyrosine-Kinase Inhibitors (TKIs).
Presenter: Miriam Ferrara
Session: Poster Display session 1
Resources:
Abstract
1302 - Safety of lorlatinib in subgroups of patients from a phase 1/2 trial
Presenter: Enriqueta Felip
Session: Poster Display session 1
Resources:
Abstract
1497 - Brigatinib (BRG) in Asian vs non-Asian patients (pts) with crizotinib (CRZ)-refractory ALK+ NSCLC in the phase 2 ALTA trial
Presenter: Dae Ho Lee
Session: Poster Display session 1
Resources:
Abstract
2349 - The safety assessment of crizotinib and alectinib from real world data of 840 ALK-inhibitor naïve patients with NSCLC harboring ALK-rearrangement (WJOG9516L).
Presenter: Kei Kunimasa
Session: Poster Display session 1
Resources:
Abstract
1120 - Brigatinib in ALK TKI-pretreated ALK+ metastatic non-small cell lung cancer (mNSCLC): the Use Via Expanded Access to Brigatinib (UVEA-Brig) study
Presenter: Silvia Novello
Session: Poster Display session 1
Resources:
Abstract
5239 - Treatment patterns and outcomes for patients (pts) with anaplastic lymphoma kinase-positive (ALK+) advanced non-small-cell lung cancer (NSCLC) in US clinical practice
Presenter: Matthew Krebs
Session: Poster Display session 1
Resources:
Abstract