Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
1 Thoracic Service and Center for Cell Engineering, Memorial Sloan Kettering Cancer
Center, New York/NY/United States of America, 2 Thoracic Service, Department of
Surgery, Memorial Sloan Kettering Cancer Center, New York/NY/United States of
America
Background: Our laboratory has translated (NCT02414269, NCT02792114)
mesothelin (MSLN), a cancer-antigen, targeted chimeric antigen receptor
(CAR) T-cell therapy to solid tumors including for lung adenocarcinoma (ADC)
patients. The goal of this study is to investigate the anti-tumor efficacy of
MSLN CAR T cells against lung ADC with heterogenous MSLN expression, and
further develop mechanistic insights to potentiate the therapy. Methods:
Human CAR T cells transduced with M28z, MSLN CAR with CD28
costimulation, were tested in vitro (cytotoxicity by 51 Cr release assay,
proliferation, cytokine secretion, LFA-1/ICAM-1 [lymphocyte function
associated antigen-1/intercellular adhesion molecule 1] adhesion assay, and
flow cytometry) and in vivo (tumor and T-cell bioluminescence imaging [BLI],
survival) against low-, high- or a mixture (50:50 or 70:30) of MSLN-expressing
A549 human lung ADC. Results: MSLN CAR T cells demonstrate antigenintensity
dependant cytotoxicity against both low- and high- MSLNexpressing
A549 cells with additive bystander cytotoxicity against 51 Crlabelled
low-MSLN A549 cells in the mixture both in vitro (Figure Panel A) and
in vivo (22 days delay in tumor progression by low-MSLN A549 cells). Flow
cytometry demonstrated ICAM-1 overexpression on low-MSLN A549 cells
when treated with effector cytokine-rich supernatant collected by exposure
of CAR T cells to high-MSLN A549 cells (Panel B), LFA-1 expression by
MSLN-activated CAR T cells (Panel B). Activated CAR T cells adherence to
ICAM-Fc coated plates compared to controls (Panel C). LFA-1/ICAM-1
expression promoted adherence of antigen-activated CAR T cells to low
antigen-expressing tumor cells (Panel D), which is inhibited in the presence of
LFA-1 blocking antibody (Panel E).
Fluoroscopy was used in all. Sampling included bronchial washing and
brushing (if no direct vision) or biopsy (if lesion directly visualized). Statistical
analyses R-3.2.3. Results: Total of 63 patients (VBN and non-VBN, 21:42).
Clinical characteristics in table 1. Diagnostic yield was 75% vs 43.9% (p=0.029).
Factors associated to positive diagnosis in table 2. Further diagnostic
techniques were needed in 14% vs 52% (p=0.001). No differences seen in
procedure duration or complications.
Conclusion: We provide a mechanistic reason for the antigen-specific,
bystander efficacy of CAR T cells against low-antigen expressing lung cancer
cells. Strategies to augment LFA-ICAM interactions between CAR T cells and
cancer cells can effectively translate mesothelin-targeted CAR T-cell therapy
against heterogenous antigen-expressing solid tumor, lung cancer.
Keywords: lung cancer, mesothelin, Immunotherapy, CAR T-cell
Conclusion: VBN significantly improves the diagnostic yield of ultrathin
bronchoscopy for diagnosing peripheral pulmonary lesions, especially those
located in the utmost periphery and fluoroscopically not visible. Therefore,
use of VBN reduces the need for further diagnostic procedures. Funded by La
MaratóTV3-20133510, FIS-ETES PI09/90917, FUCAP and SEPAR.
Keywords: Peripheral Pulmonary Nodule, bronchoscopy
SESSION MA05: INNOVATIVE TECHNIQUES IN PULMONO-
LOGY AND THE IMPACT ON LUNG CANCER
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
MA05: INNOVATIVE TECHNIQUES IN PULMONOLOGY AND THE IMPACT ON LUNG CANCER
MONDAY, DECEMBER 5, 2016 - 16:00-17:30
MA05.01 VIRTUAL BRONCHOSCOPIC NAVIGATION-GUIDED
ULTRATHIN BRONCHOSCOPY FOR DIAGNOSING PERIPHERAL
PULMONARY LESIONS
Marta Diez-Ferrer, Arturo Morales, Noelia Cubero, Rosa Lopez-Lisbona, Nikos
Koufos, Jordi Dorca, Antoni Rosell
Respiratory Medicine, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat/
Spain
Background: Diagnosis of peripheral pulmonary lesions with ultrathin
bronchoscopy (UTH) has fewer complications than transthoracic needle
aspiration (TTNA). However, diagnostic yield with UTH is lower. Virtual
bronchoscopic navigation (VBN) might increase diagnostic performance of
UTH. The main objective was to compare diagnostic yield of UTH with and
without VBN. Methods: Prospective case-control study paired 1:2 for lesion
size and localization, bronchus sign, sex and final diagnosis. LungPoint
(Broncus, USA) was used to plan and navigate based upon online image
analysis, putting endoscopic and virtual images in correspondence.
MA05.02 ELECTROMAGNETIC NAVIGATION BRONCHOSCOPY:
A PROSPECTIVE, GLOBAL, MULTICENTER ANALYSIS OF 1000
SUBJECTS WITH LUNG LESIONS
Erik Folch 1 , Javier Flandes 2 , Sandeep Khandhar 3
1 Massachusetts General Hospital, Boston/MA/United States of America,
2 Pulmonary Department, Iis-Fundacion Jimenez Diaz University Hospital, Ciberes,
Madrid/Spain, 3 CVTSA/Inova Cancer Center, Fairfax Hospital, Falls Church/VA/
United States of America
Background: Electromagnetic navigation bronchoscopy (ENB) may aid
in accessing smaller, more peripheral lesions and hence facilitate earlier
diagnosis. ENB may also provide a safer alternative to transthoracic biopsy,
and allow adequate tissue capture for molecular testing, diagnosis, staging,
and localization for surgery in a single anesthetic event. However, usage
patterns, safety, and performance remain largely unexplored in a prospective,
multicenter study. Methods: NAVIGATE is a global, prospective, multicenter
study of ENB using the superDimension navigation system (Medtronic,
Minneapolis). A pre-specified 1-month interim analysis was conducted on the
Copyright © 2016 by the International Association for the Study of Lung Cancer
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