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
5705 - External validation and longitudinal extension of the LIPI (Lung Immune Prognostic Index) for immunotherapy outcomes in advanced non-small cell lung cancer.
Presenter: Jakob Riedl
Session: Poster Display session 3
Resources:
Abstract
5758 - Changes of TCR Repertoire in Metastatic Renal Cell Carcinoma and Metastatic Melanoma Patients Treated with Nivolumab
Presenter: Martin Klabusay
Session: Poster Display session 3
Resources:
Abstract
1743 - Expression of MHC class I, HLA-A and HLA-B identifies immune activated breast tumors with favorable outcome
Presenter: María Del Mar Noblejas López
Session: Poster Display session 3
Resources:
Abstract
2219 - Prognostic Significance of Tumor Tissue NeuGcGM3 Ganglioside Expression and Predictive Value of Circulating Tumor Cell Count Monitoring in Patients Receiving Racotumomab Immunotherapy
Presenter: Necdet Üskent
Session: Poster Display session 3
Resources:
Abstract
2996 - Evolution of Myeloid-Derived Suppressor Cells and Objective Response Rate in Relapsed/Refractory Diffuse Large B Cell Lymphoma (R/R DLBCL) patients after receiving immunotherapy
Presenter: Carlos Jiménez Cortegana
Session: Poster Display session 3
Resources:
Abstract
2110 - A Phase Ia/Ib trial of the anti-programmed death-ligand 1 (PD-L1) human monoclonal antibody (mAb), CS1001, in patients (pts) with advanced solid tumors or lymphomas
Presenter: Lin Shen
Session: Poster Display session 3
Resources:
Abstract
3515 - Results from a randomised Phase 1/2 trial evaluating the safety and antitumour activity of anti-PD-1 (MEDI0680)/anti-PD-L1 (durvalumab) vs anti-PD-1 (nivolumab) alone in metastatic clear cell renal cell carcinoma (ccRCC)
Presenter: Martin Voss
Session: Poster Display session 3
Resources:
Abstract
3566 - Pembrolizumab in Advanced Rare Cancers
Presenter: Aung Naing
Session: Poster Display session 3
Resources:
Abstract
3567 - High clinical benefit rates of pembrolizumab in very rare sarcoma histotypes: first results of the AcSé Pembrolizumab study
Presenter: Jean-Yves Blay
Session: Poster Display session 3
Resources:
Abstract
2421 - Lenvatinib plus PD-1 blockade in advanced bile tract carcinoma.
Presenter: Jianzhen Lin
Session: Poster Display session 3
Resources:
Abstract