Login to Access Video or Poster Abstract: MP48-02
Sources of Funding: Kite Pharma Inc.

Introduction

The melanoma-associated antigen-A (MAGE-A) family is a highly attractive target for cancer immunotherapy because of its broad representation in cancer tissues but restricted expression in normal tissues. Recent studies have shown significant expression of MAGE A antigen in urothelial carcinoma (UC). We aim to assess MAGE A and Programmed Death-Ligand 1 (PD-L1) expression in a large UC cohort spanning multiple grades, stages, and including metastatic disease to inform immunotherapeutic approaches to the treatment of UC.

Methods

Analysis of MAGE A and PD-L1 expression on neoplastic cells using immunohistochemical staining of tissue microarrays from patients with bladder cancer (T1-4, Nx, M0-1) was done using the H-score system (a measure that simultaneously accounts for frequency and intensity of expression). We compared differential expression as well as H-scores between superficial vs. invasive, low (LG) vs. high grade (HG) as well as localized (LO) (T1-2) vs. locally advanced (LA) (T3-4) and metastatic vs non-metastatic. Comparisons between groups were done using Student’s T-test for continuous variables and Chi-Square for categorical variables.

Results

There were a total of 443 cases, of which 40% stained positively for MAGE A. Furthermore, 26% of the cohort was > 50% positive for MAGE expression. Expression was positive in 36% of the LG vs. 64% of HG patients (p=<0.001). Expression of MAGE was 48% in LO vs. 52% in LA (p=0.02). Sub-stratifying by individual stage, pT2 had the highest expression (28%) and pT4 had the lowest (2%). Mean H-score for MAGE A between HG vs. LG was 59 vs. 30, respectively (p=<0.001), Tis (15) vs. T1-4 (45) was also significant (p=<0.001). LO vs. LA was not significant (p=0.8), similarly metastatic vs. non-metastatic (p=0.59). Mean H-score for PD-L1 was significantly higher in LA vs LO (26% vs. 10% p=0.02), and in HG vs. LG (21% vs. 2% p=<0.001). No significant difference was noted between metastatic vs. non-metastatic (p=0.71). There was no significant correlation between MAGE and PD-L1 expression for HG (p=0.08) or LA (p=0.12).

Conclusions

This is the largest report of the expression of MAGE A antigen in urothelial carcinoma showing a significant expression in higher grade and stage urothelial carcinoma as well as significant proportion of patients with >50% positive expression. In conjunction with high PD-L1 expression in HG and LA these data support MAGE targeted immune interventions, including adoptive therapy with TCR engineered T cells for UC with or without combination with checkpoint inhibitor.

Funding

Kite Pharma Inc.