Data for: A cell surface-binding antibody atlas nominates a MUC18-directed antibody-drug conjugate for targeting melanoma

Shi, Jing1 ; Jiao, Tao2; Guo, Qian2; Weng, Weining1; Ma, Linjie1; Zhang, Qing1; Wang, Lijun1; Zhang, Jianjian1; Chen, Caiwei1; Huang, Yaling1; Wang, Mingqiao3; Pan, Rong3; Tang, Yanfang1; Hu, Wenhao4; Meng, Tao5; Liu, Shu-Hui1; Guo, Jun2; Kong, Yan2; Meng, Xun1

Published Sep 19, 2023 on Dryad. https://doi.org/10.5061/dryad.2280gb5zq

Data files

Sep 19, 2023 version files 56.22 MB

A375-A1_0532.txt

9.42 MB
A375-A2_0532.txt

8.58 MB
GAK-A1_0532.txt

9.82 MB
GAK-A2_0532.txt

9.47 MB
HMVII-A1_0532.txt

9.72 MB
HMVII-A2_0532.txt

9.22 MB
README.md

4.90 KB

Abstract

Recent advances in targeted therapy and immunotherapy have substantially improved the treatment of melanoma. However, therapeutic strategies are still needed for unresponsive or treatment-relapsed melanoma patients. To discover antibody-drug conjugate (ADC)-tractable cell surface targets for melanoma, we developed an atlas of melanoma cell surface binding antibodies (pAbs) using a proteome-scale antibody array platform (PETAL). Target identification of pAbs led to development of melanoma cell killing ADCs against LGR6, TRPM1, ASAP1, and MUC18, among others. MUC18 was overexpressed in both tumor cells and tumor-infiltrating blood vessels across major melanoma subtypes, making it a potential dual-compartment and universal melanoma therapeutic target. AMT-253, an MUC18-directed ADC based on topoisomerase I inhibitor exatecan and a self-immolative T moiety, had a higher therapeutic index compared to its microtubule inhibitor-based counterpart and favorable pharmacokinetics and tolerability in monkeys. AMT-253 exhibited MUC18-specific cytotoxicity through DNA damage and apoptosis and a strong bystander killing effect, leading to potent antitumor activities against melanoma cell line and patient-derived xenograft models. Tumor vasculature-targeting by a mouse MUC18-specific antibody-T1000-exatecan conjugate inhibited tumor growth in human melanoma xenografts. Combination therapy of AMT-253 with an anti-angiogenic agent generated higher efficacy than single agent in a mucosal melanoma model. Beyond melanoma, AMT-253 was also efficacious in a wide range of MUC18-expressing solid tumors. Efficient target/antibody discovery in combination with the T moiety-exatecan linker-payload exemplified here may facilitate discovery of new ADC to improve cancer treatment.

README: PETAL screening on melanoma cells

An antibody array platform (PETAL) was used to screen overexpressed surface target on melanoma cells

Description of the data and file structure

The antibody arrary was screened against 3 different cell lines: GAK, HMVII, and A375.

For each cell line, there was two antibody arrary slides: A1 and A2.

See the Methods sections for details.

The list below describes each column of data in the Results file:

Block	the block number of the feature.
Column	the column number of the feature.
Row	the row number of the feature.
Name	the name of the feature derived from the Array List (up to 40 characters long, contained in quotation marks).
ID	the unique identifier of the feature derived from the Array List (up to 40 characters long, contained in quotation marks).
X	the X-coordinate in µm of the center of the feature-indicator associated with the feature, where (0,0) is the top left of the image.
Y	the Y-coordinate in µm of the center of the feature-indicator associated with the feature, where (0,0) is the top left of the image.
Dia.	the diameter in µm of the feature-indicator.
F635 Median	median feature pixel intensity at wavelength #1 (635 nm).
F635 Mean	mean feature pixel intensity at wavelength #1 (635 nm).
F635 SD	the standard deviation of the feature pixel intensity at wavelength #1 (635 nm).
B635 Median	the median feature background intensity at wavelength #1 (635 nm).
B635 Mean	the mean feature background intensity at wavelength #1 (635 nm).
B635 SD	the standard deviation of the feature background intensity at wavelength #1 (635 nm).
% > B635 + 1 SD	the percentage of feature pixels with intensities more than one standard deviation above the background pixel intensity, at wavelength #1 (635 nm).
% > B635 + 2 SD	the percentage of feature pixels with intensities more than two standard deviations above the background pixel intensity, at wavelength #1 (635 nm).
F635 % Sat.	the percentage of feature pixels at wavelength #1 that are saturated.
F532 Median	median feature pixel intensity at wavelength #2 (532 nm).
F532 Mean	mean feature pixel intensity at wavelength #2 (532 nm).
F532 SD	the standard deviation of the feature intensity at wavelength #2 (532 nm).
B532 Median	the median feature background intensity at wavelength #2 (532 nm).
B532 Mean	the mean feature background intensity at wavelength #2 (532 nm).
B532 SD	the standard deviation of the feature background intensity at wavelength #2 (532 nm).
% > B532 + 1 SD	the percentage of feature pixels with intensities more than one standard deviation above the background pixel intensity, at wavelength #2 (532 nm).
% > B532 + 2 SD	the percentage of feature pixels with intensities more than two standard deviations above the background pixel intensity, at wavelength #2 (532 nm).
F532 % Sat.	the percentage of feature pixels at wavelength #2 that are saturated.
Ratio of Medians	the ratio of the median intensities of each feature for each wavelength, with the median background subtracted.
Ratio of Means	the ratio of the arithmetic mean intensities of each feature for each wavelength, with the median background subtracted.
Median of Ratios	the median of pixel-by-pixel ratios of pixel intensities, with the median background subtracted.
Mean of Ratios	the geometric mean of the pixel-by-pixel ratios of pixel intensities, with the median background subtracted.
Ratios SD	the geometric standard deviation of the pixel intensity ratios.
Rgn Ratio	the regression ratio of every pixel in a 2-feature-diameter circle around the center of the feature.
Rgn R²	the coefficient of determination for the current regression value.
F Pixels	the total number of feature pixels.
B Pixels	the total number of background pixels.
Circularity	a metric based on the variance of the distance of each boundary pixel to the centroid of the feature
Sum of Means	the sum of the arithmetic mean intensities for each wavelength, with the median background subtracted.
Log Ratio	log (base 2) transform of the ratio of the medians.
F532 Total Intensity	the sum of all pixel intensities in the feature.
Flags	the type of flag associated with a feature.
Normalize	the normalization status of the feature (included/not included).
Autoflag	reports whether or not a feature has been flagged from the Flag Features dialog box. It applies to good and bad flags only.

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