Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTUE541)

• DTT Name: Leukocyte surface antigen Leu-16 (CD20)
• Synonyms: Membrane-spanning 4-domains subfamily A member 1; Leu-16; Bp35; B-lymphocyte surface antigen B1; B-lymphocyte antigen CD20
• Gene Name: MS4A1
• DTT Type: Successful target; [1]
• BioChemical Class: CD20 calcium channel
• UniProt ID: CD20_HUMAN
• TTD ID: T73215
• Sequence:
  MTTPRNSVNGTFPAEPMKGPIAMQSGPKPLFRRMSSLVGPTQSFFMRESKTLGAVQIMNG
  LFHIALGGLLMIPAGIYAPICVTVWYPLWGGIMYIISGSLLAATEKNSRKCLVKGKMIMN
  SLSLFAAISGMILSIMDILNIKISHFLKMESLNFIRAHTPYINIYNCEPANPSEKNSPST
  QYCYSIQSLFLGILSVMLIFAFFQELVIAGIVENEWKRTCSRPKSNIVLLSAEEKKEQTI
  EIKEEVVGLTETSSQPKNEEDIEIIPIQEEEEEETETNFPEPPQDQESSPIENDSSP
• Function: Functions as a store-operated calcium (SOC) channel component promoting calcium influx after activation by the B-cell receptor/BCR. B-lymphocyte-specific membrane protein that plays a role in the regulation of cellular calcium influx necessary for the development, differentiation, and activation of B-lymphocytes.
• KEGG Pathway: Hematopoietic cell lineage (hsa04640)

Molecular Interaction Atlas (MIA) of This DTT

11 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Epcoritamab	DMEX86V	Diffuse large B-cell lymphoma	2A81	Approved	[2]
Glofitamab	DM45HT6	Diffuse large B-cell lymphoma	2A81	Approved	[3]
Ibritumomab	DMG594T	Non-hodgkin lymphoma	2B33.5	Approved	[4]
Mosunetuzumab	DM15ZIB	Follicular lymphoma	2A80	Approved	[5]
Obinutuzumab	DM3BVAE	Chronic lymphocytic leukaemia	2A82.0	Approved	[6]
Ocrelizumab	DMEZ2KH	Diffuse large B-cell lymphoma	2A81	Approved	[7]
Ofatumumab	DM295PR	Chronic lymphocytic leukaemia	2A82.0	Approved	[8]
Rituximab	DM1YVZT	Central nervous system non-hodgkin lymphoma		Approved	[1]
Tisagenlecleucel	DMM9BJD	Acute lymphoblastic leukaemia	2A85	Approved	[9]
Tositumomab	DMMYZ3D	Non-hodgkin lymphoma	2B33.5	Approved	[4]
Ublituximab	DMHTY9W	Multiple sclerosis	8A40	Approved	[10]

42 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MK-8808	DMT8IAJ	Follicular lymphoma	2A80	Phase 3	[11]
PF-05280586	DMNZOCK	Cluster headache	8A81.0	Phase 3	[12]
SAIT101	DMI1R5S	Follicular lymphoma	2A80	Phase 3	[13]
AME-133v	DMIVZ3M	Non-hodgkin lymphoma	2B33.5	Phase 2	[14]
ATM AVI	DM7I56B	Bacterial infection	1A00-1C4Z	Phase 2	[6]
CAR-T cells targeting CD20	DM3RU0A	Non-hodgkin lymphoma	2B33.5	Phase 2	[15]
CD20 CAR T cells	DMQGI8R	B-cell chronic lymphocytic leukaemia	2A82.00	Phase 2	[16]
DI-Leu16-IL2	DMTLB92	Non-hodgkin lymphoma	2B33.5	Phase 2	[17]
Iodine-131-tositumomab	DMNW0DG	N. A.	N. A.	Phase 2	[18]
MT-3724	DMCNL7Z	Diffuse large B-cell lymphoma	2A81	Phase 2	[19]
Odronextamab	DMP6NVV	B-cell non-hodgkin lymphoma	2B33.5	Phase 2	[20]
Plamotamab	DMOV28A	Diffuse large B-cell lymphoma	2A81	Phase 2	[21]
REGN1979	DMSJ3Z5	B-cell non-hodgkin lymphoma	2B33.5	Phase 2	[9]
SBI-087	DMSUQFJ	Multiple sclerosis	8A40	Phase 2	[22]
TRU-015	DMHEWT7	Lymphoma	2A80-2A86	Phase 2	[23]
Veltuzumab	DM5BL4C	Chronic lymphocytic leukaemia	2A82.0	Phase 2	[24]
4SCAR19 and 4SCAR20	DMFVTSG	B-cell lymphoma	2A86	Phase 1/2	[25]
Anti-CD19 and Anti-CD20 CAR-T Cells	DMLFB25	B-cell lymphoma	2A86	Phase 1/2	[26]
Anti-CD20 CAR-T cells	DM4WEZL	Diffuse large B-cell lymphoma	2A81	Phase 1/2	[27]
Anti-CD20-CAR vector-transduced autologous T cells	DMCDUJY	Acute lymphoblastic leukaemia	2A85	Phase 1/2	[28]
Anti-CD20-CAR-transduced T cells	DMXMK30	leukaemia	2A60-2B33	Phase 1/2	[29]
CART20	DMKGU5F	B-cell lymphoma	2A86	Phase 1/2	[30]
CD19 and CD20 CAR-T Cells	DMRJ3ND	B-cell lymphoma	2A86	Phase 1/2	[31]
CD20-Specific CAR T Cells	DMHPZ8G	Chronic lymphocytic leukaemia	2A82.0	Phase 1/2	[32]
FBT-A05	DMQSF5C	Chronic lymphocytic leukaemia	2A82.0	Phase 1/2	[33]
GEN3013	DMZABYH	Diffuse large B-cell lymphoma	2A81	Phase 1/2	[34]
MB-CART20.1	DMXU7P6	Non-hodgkin lymphoma	2B33.5	Phase 1/2	[35]
PBCAR20A	DM7NKWQ	Chronic lymphocytic leukaemia	2A82.0	Phase 1/2	[36]
Anti-CD19 anti-CD20 Bispecific CAR-T	DMCABUR	leukaemia	2A60-2B33	Phase 1	[37]
BM-ca	DM43RV5	Non-hodgkin lymphoma	2B33.5	Phase 1	[38]
CAR-20/19-T Cells	DM4CXE2	B-cell non-hodgkin lymphoma	2B33.5	Phase 1	[39]
CART-20 cells	DMR0Z65	Acute lymphoblastic leukaemia	2A85	Phase 1	[40]
CD20-CAR-T Cells	DM37OJN	B-cell lymphoma	2A86	Phase 1	[41]
CD20-CART	DMSJBUZ	leukaemia	2A60-2B33	Phase 1	[42]
CD20-CD19 cCAR	DMUYTW3	B-cell lymphoma	2A86	Phase 1	[43]
CD20Bi aATC	DMGXS8L	Non-hodgkin lymphoma	2B33.5	Phase 1	[44]
IGM-2323	DMMPINS	Non-hodgkin lymphoma	2B33.5	Phase 1	[45]
KITE-363	DMIZPF4	B-cell lymphoma	2A86	Phase 1	[46]
RG6035	DMAO0NI	Multiple sclerosis	8A40	Phase 1	[47]
RG7828	DMCUBZO	Haematological malignancy	2B33.Y	Phase 1	[9]
XmAb13676	DMXTOCE	B-cell lymphoma	2A86	Phase 1	[9]
Anti-CD19/20-CAR vector-transduced T cells	DM3M9OY	Acute lymphoblastic leukaemia	2A85	Clinical trial	[48]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ATA2431	DM34FEA	B-cell lymphoma	2A86	Preclinical	[49]

8 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
227Th-rituximab	DMHJM0F	Solid tumour/cancer	2A00-2F9Z	Investigative	[6]
2LM20-4	DMZD348	Autoimmune diabetes	5A10	Investigative	[6]
Anti-CD-20 mab	DMCYOPR	Discovery agent	N.A.	Investigative	[6]
Anti-CD20 engineered toxin bodies	DMEHRKA	Lymphoma	2A80-2A86	Investigative	[6]
BLX-301	DM728RW	Non-hodgkin lymphoma	2B33.5	Investigative	[6]
BVX-20-CD20	DMAVDNU	Non-hodgkin lymphoma	2B33.5	Investigative	[6]
DXL-625	DMZWAQ3	Chronic lymphocytic leukaemia	2A82.0	Investigative	[6]
MEDI-552	DMQ5S9C	Discovery agent	N.A.	Investigative	[50]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Rheumatoid arthritis	FA20	Synovial tissue	4.00E-02	0.25	0.56

References

• [1] [Contribution of radioimmunotherapy to the treatment of lymphoma]. Ann Pharm Fr. 2008 Nov-Dec;66(5-6):300-8.
• [2] Clinical pipeline report, company report or official report of Genmab.
• [3] Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell-Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial. J Clin Oncol. 2021 Jun 20;39(18):1959-1970.
• [4] Structure of the Fab fragment of therapeutic antibody Ofatumumab provides insights into the recognition mechanism with CD20. Mol Immunol. 2009 Jul;46(11-12):2419-23.
• [5] Mitigating the risk of cytokine release syndrome in a Phase I trial of CD20/CD3 bispecific antibody mosunetuzumab in NHL: impact of translational system modeling. NPJ Syst Biol Appl. 2020 Aug 28;6(1):28.
• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2628).
• [7] Emerging drugs for rheumatoid arthritis. Expert Opin Emerg Drugs. 2008 Mar;13(1):175-96.
• [8] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] The optimized anti-CD20 monoclonal antibody ublituximab bypasses natural killer phenotypic features in Waldenstr m macroglobulinemia. Haematologica. 2015 Apr;100(4):e147-51.
• [11] Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance. Oncogene. 2003 Oct 20;22(47):7359-68.
• [12] Comparative nonclinical assessments of the proposed biosimilar PF-05280586 and rituximab (MabThera ). Toxicol Pathol. 2014 Oct;42(7):1069-81.
• [13] Past, Present, and Future of Rituximab-The World's First Oncology Monoclonal Antibody Therapy. Front Oncol. 2018 Jun 4;8:163.
• [14] Results of a phase 1 study of AME-133v (LY2469298), an Fc-engineered humanized monoclonal anti-CD20 antibody, in FcgammaRIIIa-genotyped patients with previously treated follicular lymphoma. Clin Cancer Res. 2012 Mar 1;18(5):1395-403.
• [15] ClinicalTrials.gov (NCT03196830) CAR-T for R/R B-NHL
• [16] ClinicalTrials.gov (NCT02846584) a Clinical Research of Sequential CAR-T Bridging HSCT in the Treatment of Relapse/Refractory B-cell Malignancies
• [17] National Cancer Institute Drug Dictionary (drug id 599668).
• [18] Rituximab blocks binding of radiolabeled anti-CD20 antibodies (Ab) but not radiolabeled anti-CD45 Ab. Blood. 2008 Aug 1;112(3):830-5.
• [19] Clinical pipeline report, company report or official report of Molecular Templates.
• [20] Odronextamab, a human CD20*CD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. Lancet Haematol. 2022 May;9(5):e327-e339.
• [21] Plamotamab (XmAb(?)13676) for Ibrutinib- refractory CXCR4-mutated extramedullary Waldenstr?m macroglobulinemia. Leuk Lymphoma. 2022 Mar;63(3):738-742.
• [22] Translational Mini-Review Series on B Cell-Directed Therapies: Recent advances in B cell-directed biological therapies for autoimmune disorders. Clin Exp Immunol. 2009 August; 157(2): 198-208.
• [23] TRU-015, a small modular immunopharmaceutical (SMIP drug candidate directed against CD20, demonstrates clinical improvement in subjects with rheumatoid arthritis. Arthritis Res Ther. 2007; 9(Suppl 3): P32.
• [24] Veltuzumab, an anti-CD20 mAb for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and immune thrombocytopenic purpura. Curr Opin Mol Ther. 2009 Apr;11(2):200-7.
• [25] ClinicalTrials.gov (NCT03125577) Combination CAR-T Cell Therapy Targeting Hematological Malignancies
• [26] ClinicalTrials.gov (NCT03207178) Sequential Infusion of Anti-CD19 and Anti-CD20 CAR-T Cells Against Relapsed and Refractory B-cell Lymphoma
• [27] ClinicalTrials.gov (NCT02737085) the Sequential Therapy of CD19-targeted and CD20-targeted CAR-T Cell Therapy for Diffuse Large B Cell Lymphoma(DLBCL)
• [28] ClinicalTrials.gov (NCT01735604) Genetically Engineered Lymphocyte Therapy in Treating Patients With Lymphoma That is Resistant or Refractory to Chemotherapy
• [29] ClinicalTrials.gov (NCT02710149) A Clinical Research of CD20-Targeted CAR-T in B Cell Malignancies
• [30] ClinicalTrials.gov (NCT02965157) Pilot Study of Anti-CD20-CAR-engineered T Cells in Patients With Chemotherapy Resistant or Refractory CD20+ Lymphoma
• [31] ClinicalTrials.gov (NCT03398967) A Feasibility and Safety Study of Universal Dual Specificity CD19 and CD20 or CD22 CAR-T Cell Immunotherapy for Relapsed or Refractory Leukemia and Lymphoma
• [32] ClinicalTrials.gov (NCT03277729) A Phase I/II Study to Evaluate the Safety of Cellular Immunotherapy Using Autologous T Cells Engineered to Express a CD20-Specific Chimeric Antigen Receptor for Patients With Relapsed or Refractory B Cell Non-Hodgkin Lymphomas
• [33] Immunotherapy with FBTA05 (Bi20), a trifunctional bispecific anti-CD3 x anti-CD20 antibody and donor lymphocyte infusion (DLI) in relapsed or refractory B-cell lymphoma after allogeneic stem cell transplantation: study protocol of an investigator-driven, open-label, non-randomized, uncontrolled, dose-escalating Phase I/II-trial. J Transl Med. 2013 Jul 2;11:160.
• [34] DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing. EBioMedicine. 2020 Feb;52:102625.
• [35] ClinicalTrials.gov (NCT03664635) MB-CART20.1 Lymphoma
• [36] Clinical pipeline report, company report or official report of Precision Biosciences.
• [37] ClinicalTrials.gov (NCT03271515) Immunotherapy With Bispecific CAR-T Cells for B-Cell Lymphoma, ALL and CLL
• [38] BM-ca is a newly defined type I/II anti-CD20 monoclonal antibody with unique biological properties. Int J Oncol. 2011 Feb;38(2):335-44.
• [39] ClinicalTrials.gov (NCT03375619) Long-term Follow-up Study of Patients Receiving CAR-20/19-T Cells
• [40] ClinicalTrials.gov (NCT03291444) CAR-T Cells Combined With Peptide Specific Dendritic Cell in Relapsed/Refractory Leukemia/MDS
• [41] ClinicalTrials.gov (NCT03576807) The Clinical Research of Anti-CD20 CAR-T Cells in Patients With Refractory or Relapsed B Lymphocyte Lymphoma
• [42] ClinicalTrials.gov (NCT03407859) Sequential Treatment With CD20/CD22/CD10-CART After CD19-CART Treatment Base on MRD in Relapsed/Refractory B-ALL
• [43] Clinical pipeline report, company report or official report of iCell Gene Therapeutics.
• [44] CD20-Targeted T Cells after Stem Cell Transplantation for High Risk and Refractory Non-Hodgkin's Lymphoma. Biol Blood Marrow Transplant. 2013 June; 19(6): 925-933.
• [45] Clinical pipeline report, company report or official report of IGM Biosciences.
• [46] Clinical pipeline report, company report or official report of Gilead
• [47] Clinical pipeline report, company report or official report of Roche
• [48] ClinicalTrials.gov (NCT03097770) Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by Tandem CAR T Cells Targeting CD19 and CD20
• [49] Clinical pipeline report, company report or official report of Atara Biotherapeutics.
• [50] Anti CD37 antibodies