Payload ID	PAY0WCEKW
Name	Pseudomonas exotoxin PE38
Synonyms	Pseudomonas exotoxin PE38    Click to Show/Hide
Target	Eukaryotic elongation factor 2 kinase (EEF2K)					Target Info

Standard Type	Value	Units	Cell line	Disease Model	Cell line ID	Reference
Half-maximal effective concentration (EC50)	3.311	ng/mL	CCRF-CEM cells	T acute lymphoblastic leukemia	CVCL_0207	[1]
Half-maximal effective concentration (EC50)	3.479	ng/mL	Acute lymphoblastic leukemia cells	Acute lymphoblastic leukemia	Undisclosed	[1]
Half-maximal effective concentration (EC50)	5.998	ng/mL	Jurkat cells	T acute lymphoblastic leukemia	CVCL_0065	[1]

Experiment 1 Reporting the Activity Date of This ADC					[2]
Patients Enrolled	Eligible patients must have metastatic/unresectable solid tumors (measurable per RECIST 1.1), ≥1 prior systemic therapy, ECOG 0-1, and adequate organ function. Key exclusions include active CNS metastases (unless stable post-radiation), uncontrolled cardiac conditions, prior toxin-directed therapy, or hypersensitivity to dCD133KDEL components. Women of childbearing potential must use dual contraception.    Click to Show/Hide
Administration Dosage	Patients will receive dCD133KDEL at the assigned dose level via a 30-minute intravenous infusion on days 1, 3, 5, 8, 10 and 12 (total of 6 doses) of a 28-day cycle.
Related Clinical Trial
NCT Number	NCT02845414	Phase Status	PHASE1
Clinical Description	Phase I Study Of Stem-Cell Directed Deimmunized CD133KDEL Toxin In The Treatment Of Solid Tumors
Primary Endpoint	The primary objective is to determine the maximum tolerated dose (MTD) of dCD133KDEL by Day 28, with dose-limiting toxicities (DLTs) defined as ≥Grade 3 adverse events (CTCAE v4.0) within 21 days post-first dose that are possibly treatment-related.
Other Endpoint	Secondary objectives include tumor response assessment per RECIST 1.1 criteria (evaluated between Days 29-33 and every 6-12 weeks thereafter), with responses summarized by dose level including 95% confidence intervals.

Experiment 1 Reporting the Activity Date of This ADC					[3]
Patients Enrolled	Key disease criteria include histologically confirmed CNS/extraneural tumors with ≥30% B3 antibody reactivity in CSF/tumor cells. Patient requirements: age ≥18, Karnofsky 50-100%, adequate hematologic/renal/hepatic function
Related Clinical Trial
NCT Number	NCT00003020	Phase Status	PHASE1
Clinical Description	Protocol for a Phase I Study of Intrathecal LMB-7 (Single-Chain Immunotoxin Constructed From Monoclonal Antibody B3-Pseudomonas Exotoxin PE 38) [IND 5863, NSC 658931] in the Treatment of Patients With Leptomeningeal Neoplasms
Experiment 2 Reporting the Activity Date of This ADC					[4]
Patients Enrolled	Patients with leptomeningeal metastases.
Related Clinical Trial
NCT Number	NCT00003020	Phase Status	Phase 1
Clinical Description	Phase 1 dose-escalation study of intravenous CMD-193 in subjects with advanced malignant solid tumors.

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 0.81%	Positive HER2 expression (HER2 +++/++)
Method Description	N87 tumors were implanted to NOD/SCID mice to the size of about 100 mm3 (day 0) and were then treated with ADCs at day 0, day 3 and day 7 at the dosage of 0.166 mg/kg.
In Vivo Model	NCI-N87 CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3.7 pM	Positive HER2 expression (HER2 +++/++)
Method Description	N87 cells (10000) were seeded in 96-well plates for the IC50 measurements of cell viability. After incubation at 37°C for 16 h, the medium was replaced by fresh normal medium with serum and the cytotoxicity was assessed using the WST-1 reagent after 72 h of incubation at 37°C.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 2.97%	Positive HER2 expression (HER2 +++/++)
Method Description	N87 tumors were implanted to NOD/SCID mice to the size of about 100 mm3 (day 0) and were then treated with ADCs at day 0, day 3 and day 7 at the dosage of 0.166 mg/kg.
In Vivo Model	NCI-N87 CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 10.94%	Positive HER2 expression (HER2 +++/++)
Method Description	N87 tumors were implanted to NOD/SCID mice to the size of about 100 mm3 (day 0) and were then treated with ADCs at day 0, day 3 and day 7 at the dosage of 0.166 mg/kg.
In Vivo Model	NCI-N87 CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	16.7 pM	Positive HER2 expression (HER2 +++/++)
Method Description	N87 cells (10000) were seeded in 96-well plates for the IC50 measurements of cell viability. After incubation at 37°C for 16 h, the medium was replaced by fresh normal medium with serum and the cytotoxicity was assessed using the WST-1 reagent after 72 h of incubation at 37°C.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 4.32%	Positive HER2 expression (HER2 +++/++)
Method Description	N87 tumors were implanted to NOD/SCID mice to the size of about 100 mm3 (day 0) and were then treated with ADCs at day 0, day 3 and day 7 at the dosage of 0.166 mg/kg.
In Vivo Model	NCI-N87 CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	7.3 pM	Positive HER2 expression (HER2 +++/++)
Method Description	N87 cells (10000) were seeded in 96-well plates for the IC50 measurements of cell viability. After incubation at 37°C for 16 h, the medium was replaced by fresh normal medium with serum and the cytotoxicity was assessed using the WST-1 reagent after 72 h of incubation at 37°C.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 13%	Positive HER2 expression (HER2 +++/++)
Method Description	N87 tumors were implanted to NOD/SCID mice to the size of about 100 mm3 (day 0) and were then treated with ADCs at day 0, day 3 and day 7 at the dosage of 0.166 mg/kg.
In Vivo Model	NCI-N87 CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3 pM	Positive HER2 expression (HER2 +++/++)
Method Description	N87 cells (10000) were seeded in 96-well plates for the IC50 measurements of cell viability. After incubation at 37°C for 16 h, the medium was replaced by fresh normal medium with serum and the cytotoxicity was assessed using the WST-1 reagent after 72 h of incubation at 37°C.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 18.19%	Positive HER2 expression (HER2 +++/++)
Method Description	N87 tumors were implanted to NOD/SCID mice to the size of about 100 mm3 (day 0) and were then treated with ADCs at day 0, day 3 and day 7 at the dosage of 0.166 mg/kg.
In Vivo Model	NCI-N87 CDX model
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	33 pM	Positive HER2 expression (HER2 +++/++)
Method Description	N87 cells (10000) were seeded in 96-well plates for the IC50 measurements of cell viability. After incubation at 37°C for 16 h, the medium was replaced by fresh normal medium with serum and the cytotoxicity was assessed using the WST-1 reagent after 72 h of incubation at 37°C.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Experiment 1 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	19.98 ug/mL	Positive HER2 expression (HER2 +++/++)
Method Description	The cytotoxic effect of recombinant proteins was evaluated by the MTT assay using SKBR-3 and MCF-7 cells.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033
Experiment 2 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 100 ug/mL	Low HER2 expression (HER2 -)
Method Description	The cytotoxic effect of recombinant proteins was evaluated by the MTT assay using SKBR-3 and MCF-7 cells.
In Vitro Model	Invasive breast carcinoma	MCF-7 cells		CVCL_0031

Ref 1	Humanized CD7 nanobody-based immunotoxins exhibit promising anti-T-cell acute lymphoblastic leukemia potential. Int J Nanomedicine. 2017 Mar 13;12:1969-1983.
Ref 2	Study of CD133KDEL Toxin in the Treatment for Solid Tumors
Ref 3	LMB-7 Immunotoxin in Treating Patients With Leptomeningeal Metastases
Ref 4	Protocol for a Phase I Study of Intrathecal LMB-7 (Single-Chain Immunotoxin Constructed From Monoclonal Antibody B3-Pseudomonas Exotoxin PE 38) [IND 5863, NSC 658931] in the Treatment of Patients With Leptomeningeal Neoplasms
Ref 5	Antibody-drug conjugates with HER2-targeting antibodies from synthetic antibody libraries are highly potent against HER2-positive human gastric tumor in xenograft models. MAbs. 2019 Jan;11(1):153-165. doi: 10.1080/19420862.2018.1541370. Epub 2018 Nov 8.
Ref 6	Breast cancer targeted/ therapeutic with double and triple fusion Immunotoxins. J Steroid Biochem Mol Biol. 2020 Jun;200:105651. doi: 10.1016/j.jsbmb.2020.105651. Epub 2020 Mar 5.