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
5519 - Is there a difference of Palliative care problems and needs between cancer and non-cancer hospitalized elderly patients?
Presenter: Ioanna Chatzi
Session: Poster Display session 1
Resources:
Abstract
2505 - There is a lack of clinical research for patients with cancer in palliative care
Presenter: Marie Vinches
Session: Poster Display session 1
Resources:
Abstract
5273 - Specialist Palliative Care (SPC) in Haematological Malignancy: Establishing practices in a UK Tertiary Cancer Centre (TCC)
Presenter: Emma Kedgley
Session: Poster Display session 1
Resources:
Abstract
5864 - Evaluation of the relationship between the attachment styles and psychological resilience of cancer patients receiving chemotherapy
Presenter: Fatma Bugdayci Basal
Session: Poster Display session 1
Resources:
Abstract
770 - Gefitinib along with Methotrexate as palliative therapy in PS 3 and above in metastatic squamous cell carcinoma head and neck cancer patients
Presenter: Vidya Dusi
Session: Poster Display session 1
Resources:
Abstract
4232 - High intensity end-of-life care in pediatrics, adolescent and young adult patients with cancer using an administrative database.
Presenter: Seiko Bun
Session: Poster Display session 1
Resources:
Abstract
4845 - Embedded outpatient palliative care service within the oncology clinic: Preliminary experience in Hacettepe Oncology Hospital
Presenter: Deniz Can Guven
Session: Poster Display session 1
Resources:
Abstract
3270 - Internet-based stepped care for individuals with cancer and concurrent anxiety or depression symptoms – results from a randomized controlled trial
Presenter: Birgitta Johansson
Session: Poster Display session 1
Resources:
Abstract
5503 - Impact of Cognitive-Behavioral-Therapy (CBT) on levels of anxiety, depression and distress in cancer patients (pts)
Presenter: Daniela Tregnago
Session: Poster Display session 1
Resources:
Abstract
5553 - Cytokine genetic variations and worse quality of life among family caregivers of head and neck cancer patients in palliative care
Presenter: Daniel Pequeno
Session: Poster Display session 1
Resources:
Abstract