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
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