Abstract 1757
Background
Cancer is known to be the second cause of death worldwide. Vascular endothelial growth factors (VEGFs) regulate blood vessel development, the overexpressed of VEGF/VEGFR2 are often associated with angiogenesis, invasion, metastasis and prognosis in cancers. Targeting VEGFR2 by monoclonal antibodies has been associated with a survival benefit across multiple malignancies including lung, gastric and colorectal cancers. In addition to anti-VEGFR2 targeted therapies, immunotherapy including checkpoint blockade, adoptive cell therapy, and chimeric antigen receptor T cell (CART) acts as potential strategies to cure cancer. In this study, we propose VEGFR2-CART as a potential therapeutic strategy for different solid tumors treatment, and its therapeutic efficacy will be further investigated and verified.
Methods
In this study, the anti-VEGFR2 single chain fragment variable (scFv) antibodies were screened by using an automated high throughput phage display system. The binding affinity various CDR sequences to VEGFR2 determined by binding ELISA. We generated CART by transducing human PBMCs with a VEGFR2-CAR 2nd generation lentiviral vector. Cytotoxic ability of the generated CART was assessed by a LDH cytotoxicity assay. To evaluate the biologic effect of VEGFR2-CART cells, a breast xenograft model was performed by injecting HCC1428 cells subcutaneously into the flank of NOD/SCID mice.
Results
Seventy-two VEGFR2 clones with various CDR sequences with the range of binding affinities of 10-8 to 10-10 M were selected. Cell toxicity assays showed that 50∼60% of VEGFR2-overexpressed FS293 cells were killed by VEGFR2-CART cells. To evaluate the biologic effect of VEGFR2-CART cells, a breast xenograft model was performed by injecting HCC1428 cells subcutaneously into the flank of NOD/SCID mice. The results demonstrate that the VEGFR2-CART cells significantly inhibit the growth of HCC1428 due to reduced tumor sizes and weights.
Conclusions
The cytotoxicity assay showed that the VEGFR2-overexpressed FS293 cells were apparently killed by VEGFR2-CART cells. The antitumor effects of the VEGFR2-CART cells have been proved in a murine tumor model, suggesting that targeting VEGFR2 with CART cells can be a novel strategy in cancer immunotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Development Center for Biotechnology.
Funding
The government of the Republic of China (Taiwan).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5103 - CANOPY phase 3 program: Three studies evaluating canakinumab in patients with non-small cell lung cancer (NSCLC)
Presenter: Luis Paz-Ares
Session: Poster Display session 1
Resources:
Abstract
3666 - The Elderly Patient Individualized Chemotherapy (EPIC) trial, a study for an aged population of non-small cell lung cancer.
Presenter: Francesco Passiglia
Session: Poster Display session 1
Resources:
Abstract
4799 - KEYNOTE-495/KeyImPaCT: A Randomized, Biomarker-Directed, Phase 2 Trial of Pembrolizumab-Based Therapy for Non–Small Cell Lung Cancer (NSCLC)
Presenter: Martin Gutierrez
Session: Poster Display session 1
Resources:
Abstract
6035 - Safety, tolerability and activity of autologous T cells with enhanced T-cell receptors specific to NY ESO 1/LAGE 1a (GSK3377794) alone, or in combination with pembrolizumab, in advanced non small cell lung cancer: A Phase 1b/2a randomised pilot study
Presenter: Karen Reckamp
Session: Poster Display session 1
Resources:
Abstract
2176 - IFCT-1701 DICIPLE: a randomized phase 3 trial comparing continuation Nivolumab-Ipilimumab doublet immunotherapy until progression versus observation in patients with PDL1-positive stage IV Non-Small Cell Lung Cancer (NSCLC) after Nivolumab-Ipilimumab induction treatment
Presenter: Gerard Zalcman
Session: Poster Display session 1
Resources:
Abstract
2352 - ATALANTE-1 randomized phase 3 trial, OSE-2101 versus standard treatment as second or third line in HLA-A2 positive advanced non-small cell lung cancer (NSCLC) patients
Presenter: Enriqueta Felip
Session: Poster Display session 1
Resources:
Abstract
2451 - Phase Ib dose-escalation/expansion study of BI 836880, a VEGF/Ang2-blocking nanobody®, in combination with BI 754091, an anti-PD-1 antibody, in patients with advanced solid tumours
Presenter: Nicolas Girard
Session: Poster Display session 1
Resources:
Abstract
4285 - Radiosurgery followed by Tumor Treating Fields (TTFields) for brain metastases (1-10) from NSCLC in the phase 3 METIS trial
Presenter: Minesh Mehta
Session: Poster Display session 1
Resources:
Abstract
4909 - Nivolumab plus ipilimumab (NI) versus chemotherapy plus nivolumab (CN) in squamous cell lung cancer (SqCLC): the SQUINT trial
Presenter: Lorenza Landi
Session: Poster Display session 1
Resources:
Abstract
4125 - DUBLIN-3, a Stage IIIb/IV NSCLC Phase (Ph)3 Trial Comparing the Plinabulin (P)/Docetaxel(D) Combination with D Alone
Presenter: Ramon Mohanlal
Session: Poster Display session 1
Resources:
Abstract