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
5189 - Association between serum HGF levels and neutrophil counts in small cell lung cancer and their impact on survival
Presenter: Laura Moliner
Session: Poster Display session 1
Resources:
Abstract
3539 - Prognostic role of RLF/MYCL1 and circPVT1 in SCLC.
Presenter: Clelia Tiziana Storlazzi
Session: Poster Display session 1
Resources:
Abstract
3438 - High-biologically effective dose radiotherapy improve the survival of small cell lung cancer patients with brain metastases: a propensity-matching analysis
Presenter: Qingyang Zhuang
Session: Poster Display session 1
Resources:
Abstract
3232 - Phase 1 open-label study evaluating the safety, pharmacokinetics, and preliminary efficacy of ABBV-181 and rovalpituzumab tesirine (ROVA-T) in patients with small cell lung cancer
Presenter: Emiliano Calvo
Session: Poster Display session 1
Resources:
Abstract
3633 - Activity of the novel Aurora kinase B inhibitor AZD2811 in biomarker-defined models of small cell lung cancer
Presenter: Carminia Maria Della Corte
Session: Poster Display session 1
Resources:
Abstract
3745 - Multi-level proteomics identifies FABP5 as a primary chemoresistance mediator in extensive-stage small cell lung cancer
Presenter: Yamei Chen
Session: Poster Display session 1
Resources:
Abstract
5049 - CLEPSIDRA trial: a pilot, biomarker-guided study to assess safety, tolerability, dose finding and efficacy of iadademstat in combination with platinum-etoposide in patients with relapsed, extensive-stage small cell lung cancer
Presenter: Alejandro Navarro Mendivil
Session: Poster Display session 1
Resources:
Abstract
5997 - Phased Avelumab combined with chemotherapy as first-line treatment for patients with advanced small-cell lung cancer (SCLC): The PAVE study, a Hellenic Cooperative Oncology Group Study
Presenter: Helena Linardou
Session: Poster Display session 1
Resources:
Abstract
4502 - Tobacco use in lung cáncer (LC) patients (p) in Spain
Presenter: Enric Carcereny Costa
Session: Poster Display session 1
Resources:
Abstract
4369 - Biomarker testing of lung cancer in Spain
Presenter: Delvys Rodriguez Abreu
Session: Poster Display session 1
Resources:
Abstract