Abstract 3338
Background
Cell therapies have transformed the field of hematologic cancers, but treatment of solid tumours remains challenging. Emerging evidence suggests that T cell receptor (TCR)- engineered T cells targeting NY-ESO-1 hold promise for patients with solid tumours. NY-ESO-1 (CTAG1B) and LAGE1A (CTAG2) are tumour associated antigens (TAA) that share the SLLMWITQC peptide bound to human leukocyte antigen HLA-A*02 and are expressed in various cancers. GSK3377794 are autologous T cells engineered to express an affinity enhanced NY-ESO-1c259 TCR recognizing the SLLMWITQC/HLA-A*02 complex. Cell therapy trials using NY-ESO-1c259 TCR have shown promising efficacy in patients with synovial sarcoma, metastatic melanoma and multiple myeloma. Recently, a separate study using T cells targeted to NY-ESO-1 resulted in a partial response in a patient with advanced lung adenocarcinoma. This study aims to assess: 1) the prevalence of NY-ESO-1 and LAGE1A in various malignancies 2) GSK3377794 function against various tumours and 3) means to selectively modulate TAA expression in tumours to increase potential patient benefit.
Methods
Gene and transcript level RNAseq data for NY-ESO-1 and LAGE1A respectively, were extracted from TCGA B38 using ArrayStudio v10. A solid tumour biobank was established. HLA-A*02 expression was confirmed by flow cytometry and NY-ESO-1/LAGE1A levels were measured via qRT-PCR. Epigenetic modifiers were applied to increase TAA expression in tumours in vitro and in vivo. GSK3377794 anti-tumour function was determined by IFN-γ secretion.
Results
NY-ESO-1 and LAGE1A expression varied across malignancies and disease stages. Prevalence is high in synovial sarcoma and multiple myeloma (60-70%) and lower in lung cancer (12-15%). IFN-γ production by GSK3377794 positively correlates with antigen expression. Treatment with epigenetic modifiers lead to increased NY-ESO-1/LAGE1A expression in nonimmunogenic lung tumours, enhancing specific targeting by GSK3377794.
Conclusions
To date this is the most comprehensive analysis, using a set of clinically relevant sample specimens, that correlates antigen expression levels with functional responses of GSK3377794 in solid tumors. Epigenetic modifiers can improve GSK3377794 anti-tumour effect in lung cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
GlaxoSmithKline.
Funding
GlaxoSmithKline.
Disclosure
I. Eleftheriadou: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. S. Brett: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. A. Domogala: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. L. Patasic: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. M.A. Kijewska: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. K. Soor: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. M. Georgouli: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. J. Dopierala: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. P. Fisher: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. J. Jing: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. J. Euesden: Full / Part-time employment: GlaxosmithKline. K.R. Auger: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. R. Roberts: Full / Part-time employment: GlaxosmithKline. S. O’Sullivan: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. L. Castelletti: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. M. Damm: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. D. Pankov: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. L.A. Johnson: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. A. Shalabi: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline. C. Britten: Shareholder / Stockholder / Stock options, Full / Part-time employment: GlaxosmithKline.
Resources from the same session
1122 - Platelets from metastatic cancer patients have increased aggregation and activation
Presenter: Meera Chauhan
Session: Poster Display session 3
Resources:
Abstract
2671 - Luminal B breast cancer prognosis prediction by comprehensive analysis of Homeobox genes
Presenter: Ayako Nakashoji
Session: Poster Display session 3
Resources:
Abstract
2650 - Long non-coding RNA E2F4as promotes tumor progression and predicts patient prognosis in human ovarian cancer
Presenter: Sun-Ae Park
Session: Poster Display session 3
Resources:
Abstract
1462 - FGF19 promotes esophageal squamous cell carcinoma progression by inhibiting autophagy
Presenter: Lisha Ying
Session: Poster Display session 3
Resources:
Abstract
5787 - Proof of concept on the role of ex vivo lung cancer spheroids, cytokines expression and PBMCs profiling in monitoring disease history and response to treatments.
Presenter: Raimondo Di Liello
Session: Poster Display session 3
Resources:
Abstract
5253 - Circulating microRNAs related to DNA damage response as predictors of survival in metastatic non- small cell lung cancer patients treated with platinum-based chemotherapy
Presenter: Dimitris Mavroudis
Session: Poster Display session 3
Resources:
Abstract
5286 - Prognostic value of CTCs in advanced NSCLC patients treated with platinum-based chemotherapy
Presenter: Silvia Calabuig-Fariñas
Session: Poster Display session 3
Resources:
Abstract
5781 - Exosomes in NSCLC as a source of biomarkers
Presenter: Elena Duréndez
Session: Poster Display session 3
Resources:
Abstract
1447 - The role of Pim-1 in the development and progression of papillary thyroid carcinoma
Presenter: Xin Zhu
Session: Poster Display session 3
Resources:
Abstract
1323 - Development and Validation of a RNA-Seq Based Prognostic Signature in Neuroblastoma
Presenter: Jian-Guo Zhou
Session: Poster Display session 3
Resources:
Abstract