Antibody Information

Antibody Information

Prof. Feng ZHU (zhufeng@zju.edu.cn)

Prof. Xiaowu DONG (dongxw@zju.edu.cn)

Prof. Luo FANG (fangluo@zjcc.org.cn)

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General Information of This Antibody

Antibody ID	ANI0WWODM
Antibody Name	Camidanlumab
Organization	Genmab A/S; ADC Therapeutics SA
Indication	Non-Hodgkin's lymphoma; Acute lymphocytic leukemia
Synonyms	HuMax-TAC; ADCT-301 (unconjugated) Click to Show/Hide
Antibody Type	Monoclonal antibody (mAb)
Antibody Subtype	Humanized IgG1-kappa
Antigen Name	Interferon-stimulated gene 20 kDa protein (ISG20)	Antigen Info
ChEMBI ID	CHEMBL4297237
Click to Show/Hide the Sequence Information of This Antibody
Heavy Chain Sequence	QVQLVQSGAEVKKPGSSVKVSCKASGGTFSRYIINWVRQAPGQGLEWMGRIIPILGVENY AQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARKDWFDYWGQGTLVTVSSASTKG PSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSL SSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFL FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRV VSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQ VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNV FSCSVMHEALHNHYTQKSLSLSPGK Click to Show/Hide
Heavy Chain Varible Domain	QVQLVQSGAEVKKPGSSVKVSCKASGGTFSRYIINWVRQAPGQGLEWMGRIIPILGVENY AQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARKDWFDYWGQGTLVTVSS Click to Show/Hide
Heavy Chain Constant Domain 1	ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRV Click to Show/Hide
Heavy Chain Constant Domain 2	APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAK Click to Show/Hide
Heavy Chain Constant Domain 3	GQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDS DGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK Click to Show/Hide
Heavy Chain Hinge Region	EPKSCDKTHTCPPCP Click to Show/Hide
Heavy Chain CDR 1	GGTFSRYI Click to Show/Hide
Heavy Chain CDR 2	IIPILGVE Click to Show/Hide
Heavy Chain CDR 3	ARKDWFDY Click to Show/Hide
Light Chain Sequence	EIVLTQSPGTLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGGGTKVEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
Light Chain Varible Domain	EIVLTQSPGTLSLSPGERATLSCRASQSVSSYLAWYQQKPGQAPRLLIYGASSRATGIPD RFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGGGTKVEIK Click to Show/Hide
Light Chain Constant Domain	RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Click to Show/Hide
Light Chain CDR 1	QSVSSY Click to Show/Hide
Light Chain CDR 2	GAS Click to Show/Hide
Light Chain CDR 3	QQYGSSPLT Click to Show/Hide

The Activity Data of This Antibody

Each Antibody-drug Conjugate Related to This Antibody

Full Information of The Activity Data of The ADC(s) Related to This Antibody

Camidanlumab tesirine [Phase 2]

ADC Info

Identified from the Human Clinical Data

Click To Hide/Show 3 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC				[2]
Efficacy Data	Complete Remission (CR)	48.60% (In the cHL cohort, at 45 ug/kg) 35.00% (In the cHL cohort, at 30 ug/kg) 6.50% (in all patients with T-NHL) 10.00% (in all patients with T-NHL, 60 ug/kg doses) 7.10% (in all patients with T-NHL, 80 ug/kg doses) 0.00% (in all patients with T-NHL, 100 ug/kg doses)
Patients Enrolled	Relapsed or refractory classical Hodgkin lymphoma or non-Hodgkin lymphoma, an Eastern Cooperative Oncology Group performance status 0-2, who had no therapies available to them with established clinical benefit for their disease stage were enrolled.
Administration Dosage	Intravenously (3-150 ug/kg) once every 3 weeks.
*Related Clinical Trial*
NCT Number	NCT02432235	Clinical Status	Phase 1
Clinical Description	A phase 1 adaptive dose-escalation study to evaluate the tolerability, safety, pharmacokinetics, and antitumor activity of ADCT-301 in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma.
Primary Endpoint	The maximum tolerated dose was not reached. The recommended doses for expansion were 30 ug/kg and 45 ug/kg for patients with classical Hodgkin lymphoma and 80 ug/kg for patients with T-cell non-Hodgkin lymphomas. No recommended doses for expansion were defined for B-cell non-Hodgkin lymphomas.
Other Endpoint	In the cHL cohort,ORR (95% CI) was 86.49% at 45 ug/kg (32/37 patients [71.20-95.50]) and 55.00% at 30 ug/kg (11/20 patients [31.50-76.90]); 48.65% (18/37 patients) and 35.00% (7/20 patients) achieved CR. Median (95% CI) DOR for the cHL population was 6.64 months (5.06-8.11),and was 7.16 months (4.57-8.51) in patients treated at 45 ug/kg.
Experiment 2 Reporting the Activity Date of This ADC				[3]
Patients Enrolled	Antecedent myelodysplastic syndrome who received treatment with hypomethylating agents and subsequently presented with CD25-positive AmL, or patients with R/R CD25-positive acute lymphocytic leukemia (ALL) who had failed or were intolerant to any established therapy, or for whom no other treatment options were available.
Administration Dosage	Intravenously at 3-92 ug/kg once every three weeks (Q3W) or 30 or 37.50 ug/kg every week (QW).
*Related Clinical Trial*
NCT Number	NCT02588092	Clinical Status	Phase 1
Clinical Description	A phase 1, open-label, dose-escalation, multicenter study to evaluate the tolerability, safety, pharmacokinetics, and activity of ADCT 301 in patients with relapsed or refractory CD25-positive acute myeloid leukemia (AML) or CD25-positive acute lymphoblastic leukemia.
Primary Endpoint	Two patients achieved complete responses with incomplete hematologic recovery; one each at 30.00 and 37.50 ug/kg QW.
Other Endpoint	Of 16 patients with post-baseline disease assessments, two patients treated on the QW dosing regimen had a complete response (CR).
Experiment 3 Reporting the Activity Date of This ADC				[4]
Patients Enrolled	Relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma.
Administration Dosage	45 ug/kg Q3W for 2 cycles and then 30 ug/kg Q3W thereafter; intravenous administration.
*Related Clinical Trial*
NCT Number	NCT02432235	Clinical Status	Phase 1
Clinical Description	A phase 1 adaptive dose-escalation study to evaluate the tolerability, safety, pharmacokinetics, and antitumor activity of ADCT-301 in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma.
Primary Endpoint	The ORR was 40%,representing 51 responders (patients achieved a best overall response of confirmed PR).
Other Endpoint	Of the 130 patients included in the safety analysis, 27 (20.77%) experienced grade2 increased GGT, 17 (13.08%) experienced a grade2 neurologic AE,and 18 (13.85%) experienced a grade2 autoimmune AE at cycle 6.

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 9 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 11.60% (Day 21)	Moderate CD25 expression (CD25++; 76,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Karpas 299 with moderate CD25 expression (molecules per cell surface=76000). Compared with injection of vehicle (PBS), ADCT-301 administered intravenously (i.v.) at a mean tumor volume of 160 mm³ as a single dose at 0.1 mg/kg. Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	ALK-positive anaplastic large cell lymphoma	Karpas-299 cells		CVCL_1324
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 41.50% (Day 32)	High CD25 expression (CD25+++; 310,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Su-DHL-1 with high CD25 expression (molecules per cell surface=310000).ADCT-301 was administered intravenously at mean tumor volume of 155 mm³ at single doses of 0.3 mg/kg and tumor growth compared with that observed after injection of vehicle (PBS). Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	Anaplastic large cell lymphoma	SU-DHL-1 cells		CVCL_0538
Experiment 3 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 51.30% (Day 21)	High CD25 expression (CD25+++; 310,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Su-DHL-1 with high CD25 expression (molecules per cell surface=310000).ADCT-301 was administered intravenously at mean tumor volume of 155 mm³ at single doses of 0.3 mg/kg and tumor growth compared with that observed after injection of vehicle (PBS). Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	Anaplastic large cell lymphoma	SU-DHL-1 cells		CVCL_0538
Experiment 4 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 68.40% (Day 21)	Moderate CD25 expression (CD25++; 76,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Karpas 299 with moderate CD25 expression (molecules per cell surface=76000). Compared with injection of vehicle (PBS), ADCT-301 administered intravenously (i.v.) at a mean tumor volume of 160 mm³ as a single dose at 0.2 mg/kg. Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	ALK-positive anaplastic large cell lymphoma	Karpas-299 cells		CVCL_1324
Experiment 5 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 93.20% (Day 21)	Moderate CD25 expression (CD25++; 76,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Karpas 299 with moderate CD25 expression (molecules per cell surface=76000). Compared with injection of vehicle (PBS), ADCT-301 administered intravenously (i.v.) at a mean tumor volume of 160 mm³ as a single dose at 0.4 mg/kg. Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	ALK-positive anaplastic large cell lymphoma	Karpas-299 cells		CVCL_1324
Experiment 6 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.10% (Day 32)	High CD25 expression (CD25+++; 310,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Su-DHL-1 with high CD25 expression (molecules per cell surface=310000).ADCT-301 was administered intravenously at mean tumor volume of 155 mm³ at single doses of 0.6 mg/kg and tumor growth compared with that observed after injection of vehicle (PBS). Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	Anaplastic large cell lymphoma	SU-DHL-1 cells		CVCL_0538
Experiment 7 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.10% (Day 21)	Moderate CD25 expression (CD25++; 76,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Karpas 299 with moderate CD25 expression (molecules per cell surface=76000).Vechicle (PBS), ADCT-301 (dar 2.2), nonbinding ADC (DAR 2.1) or Adcetris (DAR~4) were administered intravenously at a mean Karpas 299 tumor volume of 130mm³ as single doses at 0.5 mg/kg. Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	ALK-positive anaplastic large cell lymphoma	Karpas-299 cells		CVCL_1324
Experiment 8 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.40% (Day 21)	Moderate CD25 expression (CD25++; 76,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Karpas 299 with moderate CD25 expression (molecules per cell surface=76000). Compared with injection of vehicle (PBS), ADCT-301 administered intravenously (i.v.) at a mean tumor volume of 160 mm³ as a single dose at 0.6mg/kg. Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	ALK-positive anaplastic large cell lymphoma	Karpas-299 cells		CVCL_1324
Experiment 9 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.80% (Day 21)	High CD25 expression (CD25+++; 310,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Su-DHL-1 with high CD25 expression (molecules per cell surface=310000).ADCT-301 was administered intravenously at mean tumor volume of 155 mm³ at single doses of 0.6 mg/kg and tumor growth compared with that observed after injection of vehicle (PBS). Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	Anaplastic large cell lymphoma	SU-DHL-1 cells		CVCL_0538

Revealed Based on the Cell Line Data

Click To Hide/Show 9 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	0.26 pM	Moderate CD25 expression (CD25++; 17,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	Chronic eosinophilic leukemia	EoL-1 cells		CVCL_0258
Experiment 2 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	4.96 pM	High CD25 expression (CD25+++; 310,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	Anaplastic large cell lymphoma	SU-DHL-1 cells		CVCL_0538
Experiment 3 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	17.07 pM	Moderate CD25 expression (CD25++; 76,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	ALK-positive anaplastic large cell lymphoma	Karpas-299 cells		CVCL_1324
Experiment 4 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	19.60 pM	High CD25 expression (CD25+++; 167,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	Hodgkin lymphoma	HDLM-2 cells		CVCL_0009
Experiment 5 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	> 6667.00 pM	Negative CD25 expression (CD25-; <1,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	Burkitt lymphoma	Ramos cells		CVCL_0597
Experiment 6 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	> 6667.00 pM	Negative CD25 expression (CD25-; <1,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	Burkitt lymphoma	Daudi cells		CVCL_0008
Experiment 7 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	> 6667.00 pM	Negative CD25 expression (CD25-; <1,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	T lymphocytic leukemia	HuT 78 cells		CVCL_0337
Experiment 8 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	> 6667.00 pM	Negative CD25 expression (CD25-; <1,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	Adult acute myeloid leukemia	KG-1 cells		CVCL_0374
Experiment 9 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	7.49 pM 1.11 ng/mL	Moderate CD25 expression (CD25++; 96,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	Hodgkin lymphoma	L-540 cells		CVCL_1362

References

Ref 1	Polatuzumab vedotin or pinatuzumab vedotin plus rituximab in patients with relapsed or refractory non-Hodgkin lymphoma: final results from a phase 2 randomised study (ROMULUS). Lancet Haematol. 2019 May;6(5):e254-e265.
Ref 2	Camidanlumab tesirine in patients with relapsed or refractory lymphoma: a phase 1, open-label, multicentre, dose-escalation, dose-expansion study. Lancet Haematol. 2021 Jun;8(6):e433-e445.
Ref 3	Camidanlumab tesirine, an antibody-drug conjugate, in relapsed/refractory CD25-positive acute myeloid leukemia or acute lymphoblastic leukemia: A phase I study. Leuk Res. 2020 Aug;95:106385.
Ref 4	Exposure-response analysis of Camidanlumab tesirine in patients with relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2023 Jan;91(1):1-12.
Ref 5	ADCT-301, a Pyrrolobenzodiazepine (PBD) Dimer-Containing Antibody-Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies. Mol Cancer Ther. 2016 Nov;15(11):2709-2721.

Antibody Activity Information 1

Dissociation Constant (Kd)

Antigen Expression

Positive CD25 expression (CD25+++/++)

Antibody Function

Confirm the effect of the drug conjugation with the anti-CD25 Ab on binding activity to target.

Antibody Antigen Binding Assay

Human soluble CD25-streptavidin fusion protein transiently produced in CHO cells was immobilized by amine coupling to a Biacore CM3 sensor chip. A concentration range (0.055 nmol/L) of HuMax-TAC and ADCT-301 was injected over the chip for 120 seconds as per the Biacore multi-cycle kinetics method and allowed to dissociate by running HBS-EP buffer (Hepes-buffered saline containing EDTA and surfactant P20) over the chip for 60 minutes. The equilibrium dissociation constant (KD) was calculated with BIAevaluation software.