Figure S5 from ADCT-602, a Novel PBD Dimer–containing Antibody–Drug Conjugate for Treating CD22-positive Hematologic Malignancies

Supplementary Fig. S5. Kaplan–Meier survival analysis in (A) Ramos and (B) WSU-DLCL2 xenograft models. Kaplan–Meier survival plots showing percentage animal survival (A) over 60 days in Ramos xenograft; and (B) over 59 days in WSU-DLCL2 cancer xenograft. QD once daily.</p

Figure S1 from ADCT-602, a Novel PBD Dimer–containing Antibody–Drug Conjugate for Treating CD22-positive Hematologic Malignancies

Supplementary Fig. S1. Structure and characterization of ADCT-602. (A) Full-length amino acid sequence of light and heavy chains of hLL2-C220, with the mutations C219S in the light chain and C225V and C228V in the heavy chain indicated in bold. (B) Structure of ADCT-602 with the PBD dimer payload tesirine (SG3249) conjugated at C219 of hLL2-CC20 (C220 according to the EU numbering system) in the heavy chain. (C) ADCT-602 characterized by size exclusion chromatography and by (D) reduced reversed-phase chromatography. L indicates elution of the light chain, whereas H0 and H1 indicate elution of the unconjugated H-chain or H-chain conjugated to SG3249, respectively. (E) RP-HPLC analysis of the reduced tryptic digest of 2 batches of ADCT-602 (red and black traces). Ala alanine; PABC poly(A)-binding protein C-terminal; PBD pyrrolobenzodiazepine; Val valine.</p

Figure S2 from ADCT-602, a Novel PBD Dimer–containing Antibody–Drug Conjugate for Treating CD22-positive Hematologic Malignancies

Supplementary Fig. S2. The in vitro antitumor activity of ADCT-602 does not correlate with CD22 levels in B-cell lymphomas. This figure shows a correlation of ADCT-602 IC50 values versus (A) cell surface protein expression via absolute fluorescence quantitation with Quantum Simply Cellular microspheres, (B) CD22 RNA expression levels measured via Illumina HT-12 microarrays, and (C) targeted RNA-Seq with the HTG EdgeSeq Oncology Biomarker Panel. On each plot, the x-axes are the ADCT-602 IC50 values presented as log2, and the y-axes are CD22 expression levels presented as log2. Cell lines derived from Hodgkin and T-cell lymphomas have been excluded. IC50 50% inhibitory concentration.</p

Figure S4 from ADCT-602, a Novel PBD Dimer–containing Antibody–Drug Conjugate for Treating CD22-positive Hematologic Malignancies

Supplementary Fig. S4. Time course of DNA ICL formation in KARPAS-299 cells following a 2-hour treatment with ADCT-602 or SG3199. Results are presented as a mean percentage decrease in OTM ± SD (n = 4). ICL interstrand crosslinking; OTM Olive tail moment.</p

Supplementary Data from ADCT-602, a Novel PBD Dimer–containing Antibody–Drug Conjugate for Treating CD22-positive Hematologic Malignancies

Supplementary File. Supervised analyses in B-cell lymphoma cell lines using Illumina HT-12 microarray data This file contains all data, as well as lists of transcripts upregulated (logFC+) or downregulated (logFC−) in the resistant cell lines, gene sets significantly enriched in the 2 groups of cell lines, and IRAK1 expression levels from Illumina microarray.</p

Figure S8 from ADCT-602, a Novel PBD Dimer–containing Antibody–Drug Conjugate for Treating CD22-positive Hematologic Malignancies

Supplementary Fig. S8. Quantification of cynomolgus monkey CD3+, platelets, reticulocytes, and neutrophils after dosing ADCT-602 at 0.6 or 0.9 mg/kg (2 doses, 21 days apart). Data presented as mean ± SEM (each group, n = 3). SEM standard error of mean.</p