1171P - Evaluation of the transcriptomic presence of tumor associated antigens (TAAs) from antibody drug conjugates (ADCs) and PD-L1 in melanoma: Options for new clinical opportunities

Background

Identification of tumor associated antigens (TAAs) is a main goal in order to design antibodies against tumoral cells. These antibodies can be the base for the construction of antibody drug conjugates (ADCs). It is necessary to identify indications to develop combinations of ADCs with immunotherapies including check point inhibitors (CPIs). We evaluate the transcriptional co-expression of TAAs with PD-L1 (CD274) in melanoma, to identify the best ADC to be combined with anti-PD-(L)1 therapies.

Methods

Information on all ADC TAAs in clinical development was extracted from ClinicalTrials.gov and Federal Drug Administration (FDA) website. Data from TCGA was downloaded to evaluate the expression of identified TAAs in melanoma. Correlation of every pair of genes with CD274 (PD-L1) was performed with Pearson correlation coefficients. Survival outcomes were studied with Kaplan Meier curves and hazard ratios. Tumor Immune Estimation Resource (TIMER) platform was used to investigate the association between the selected TAA and immune cell populations.

Results

32 TAAs from 123 ADCs were identified. 6 genes that coded for TAAs were upregulated in primary and metastatic melanoma compared with normal tissue, including CD22 (4.55 TMP vs 0.44 TPM), CD74 (1653.72 TPM vs 514.44 TPM), MET (13.13 TPM vs 4.44 TPM), ERBB3 (143.8 TPM vs 70.33 TPM), LIV-1 (66.01 TPM vs 32.37 TPM) and SLAMF7 (10.06 TPM vs 1.09 TPM). A positive correlation for CD74 (Rho: 0.647) and SLAMF7 (Rho: 0.65) with PD-(L)1 was observed. Expression of CD74 correlated with favorable overall survival in melanoma patients treated with any CPI (N: 397, HR: 0.52 CI 0.39-0.69, Log-rank P=3.3e-06), and for those only treated with anti-PD-1 agents (N: 325, HR: 0.52 CI 0.38-0.73, Log-rank P=7.8e-05). Similar findings were observed for SLAMF7 for any CPI (N: 397, HR: 0.5 CI 0.38-0.66, Log-rank P=3.9e-07) and anti-PD-1 (N: 325, HR: 0.53 CI 0.39-0.72, Log-rank P=4.3e-05).

Conclusions

CD74 and SLAMF7 is highly present in melanoma, correlates with PD-L1 expression and predict response to anti-PD-(L)1 therapies. This finding suggests to explore potential combinations between ADCs against these targets and anti-PD-(L)1 therapies.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.