Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTM6QSK)

• DTT Name: B-cell receptor CD22 (CD22)
• Synonyms: T-cell surface antigen Leu-14; Siglec-2; Sialic acid-binding Ig-like lectin 2; SIGLEC2; Leu-14; BL-CAM; B-lymphocyte cell adhesion molecule
• Gene Name: CD22
• DTT Type: Successful target; [1]
• BioChemical Class: Immunoglobulin
• UniProt ID: CD22_HUMAN
• TTD ID: T37539
• Sequence:
  MHLLGPWLLLLVLEYLAFSDSSKWVFEHPETLYAWEGACVWIPCTYRALDGDLESFILFH
  NPEYNKNTSKFDGTRLYESTKDGKVPSEQKRVQFLGDKNKNCTLSIHPVHLNDSGQLGLR
  MESKTEKWMERIHLNVSERPFPPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEG
  VPMRQAAVTSTSLTIKSVFTRSELKFSPQWSHHGKIVTCQLQDADGKFLSNDTVQLNVKH
  TPKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVT
  KDQSGKYCCQVSNDVGPGRSEEVFLQVQYAPEPSTVQILHSPAVEGSQVEFLCMSLANPL
  PTNYTWYHNGKEMQGRTEEKVHIPKILPWHAGTYSCVAENILGTGQRGPGAELDVQYPPK
  KVTTVIQNPMPIREGDTVTLSCNYNSSNPSVTRYEWKPHGAWEEPSLGVLKIQNVGWDNT
  TIACAACNSWCSWASPVALNVQYAPRDVRVRKIKPLSEIHSGNSVSLQCDFSSSHPKEVQ
  FFWEKNGRLLGKESQLNFDSISPEDAGSYSCWVNNSIGQTASKAWTLEVLYAPRRLRVSM
  SPGDQVMEGKSATLTCESDANPPVSHYTWFDWNNQSLPYHSQKLRLEPVKVQHSGAYWCQ
  GTNSVGKGRSPLSTLTVYYSPETIGRRVAVGLGSCLAILILAICGLKLQRRWKRTQSQQG
  LQENSSGQSFFVRNKKVRRAPLSEGPHSLGCYNPMMEDGISYTTLRFPEMNIPRTGDAES
  SEMQRPPPDCDDTVTYSALHKRQVGDYENVIPDFPEDEGIHYSELIQFGVGERPQAQENV
  DYVILKH
• Function: May be involved in the localization of B-cells in lymphoid tissues. Binds sialylated glycoproteins; one of which is CD45. Preferentially binds to alpha-2,6-linked sialic acid. The sialic acid recognition site can be masked by cis interactions with sialic acids on the same cell surface. Upon ligand induced tyrosine phosphorylation in the immune response seems to be involved in regulation of B-cell antigen receptor signaling. Plays a role in positive regulation through interaction with Src family tyrosine kinases and may also act as an inhibitory receptor by recruiting cytoplasmic phosphatases via their SH2 domains that block signal transduction through dephosphorylation of signaling molecules. Mediates B-cell B-cell interactions.
• KEGG Pathway:
  Cell adhesion molecules (CAMs) (hsa04514)
  Hematopoietic cell lineage (hsa04640)
  B cell receptor signaling pathway (hsa04662)
• Reactome Pathway:
  Antigen activates B Cell Receptor (BCR) leading to generation of second messengers (R-HSA-983695)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DTT

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Inotuzumab ozogamicin	DMAC130	Acute lymphoblastic leukaemia	2A85	Approved	[2]
Moxetumomab pasudotox	DMN63DZ	Hairy cell leukaemia	2A82.2	Approved	[3]
OspA lipoprotein	DMF5ZB3	Lyme disease	1C1G	Approved	[1]

34 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Epratuzumab	DMI1ZXV	Acute lymphoblastic leukaemia	2A85	Phase 3	[4]
BL-22	DM8R71T	Acute lymphoblastic leukaemia	2A85	Phase 2	[5]
CAR-T cells targeting CD22	DM6XN4C	Non-hodgkin lymphoma	2B33.5	Phase 2	[6]
4SCAR19 and 4SCAR22	DM8CMUW	B-cell lymphoma	2A86	Phase 1/2	[7]
4SCAR19/22 T cells	DMI8TW3	B-cell lymphoma	2A86	Phase 1/2	[8]
Anti-CD19/22-CAR vector-transduced T cells	DMMUSHR	Acute lymphoblastic leukaemia	2A85	Phase 1/2	[9]
Anti-CD22 CAR-T cells	DMY6U8R	leukaemia	2A60-2B33	Phase 1/2	[10]
Anti-CD22-CAR-transduced T cells	DMTO9VF	leukaemia	2A60-2B33	Phase 1/2	[11]
AUTO3	DMC5NSO	Acute lymphoblastic leukaemia	2A85	Phase 1/2	[12]
CART-19/22	DMX0R1E	leukaemia	2A60-2B33	Phase 1/2	[13]
CD19 and CD22 CAR-T Cells	DM581CS	B-cell lymphoma	2A86	Phase 1/2	[14]
CD19-TCRz-41BB and CD22-TCRz-41BB CAR-T Cells	DM4MBUI	Haematopoietic/lymphoid cancer	2B33.5	Phase 1/2	[15]
CD22 CAR-T	DM40NEB	B-cell lymphoma	2A86	Phase 1/2	[16]
CD22-Targeted CAR-T cells	DM61MBG	leukaemia	2A60-2B33	Phase 1/2	[17]
Anti-CD22	DMUFRDK	Haematological malignancy	2B33.Y	Phase 1	[18]
CART-22 cells	DMLGJKE	Acute lymphoblastic leukaemia	2A85	Phase 1	[19]
CART22 cells	DM6X82R	Acute lymphoblastic leukaemia	2A85	Phase 1	[20]
CART22 cells expressing anti-CD22 scFv TCRz:41BB	DMY3NWK	Acute lymphoblastic leukaemia	2A85	Phase 1	[21]
CART22-65s cells	DM4XT15	Acute lymphoblastic leukaemia	2A85	Phase 1	[22]
CART22-65s cells and huCART19 Cells	DMOJ1AH	Acute lymphoblastic leukaemia	2A85	Phase 1	[22]
CD19/CD22 CAR T cells	DMVONF0	Acute lymphoblastic leukaemia	2A85	Phase 1	[23]
CD19/CD22 CAR T-Cells	DMKA2FL	Acute lymphocytic leukaemia	2B33.3	Phase 1	[24]
CD19/CD22 Chimeric Antigen Receptor T Cells	DMPADR1	Acute lymphoblastic leukaemia	2A85	Phase 1	[25]
CD22-CART	DMHMPK1	leukaemia	2A60-2B33	Phase 1	[26]
CD22-specific CAR T-cells also expressing an EGFRt	DMP5V83	leukaemia	2A60-2B33	Phase 1	[27]
Combotox	DMA7PWX	leukaemia	2A60-2B33	Phase 1	[28]
Donor-derived CD19/22 bispecific CAR-T cells	DMZS350	leukaemia	2A60-2B33	Phase 1	[29]
JCAR018	DMR3SO5	Acute lymphoblastic leukaemia	2A85	Phase 1	[30]
JNJ-75348780	DMSDSFX	Chronic lymphocytic leukaemia	2A82.0	Phase 1	[31]
Lumoxiti	DMQI970	Hairy cell leukaemia	2A82.2	Phase 1	[32]
Patient-derived CD19- and CD22 specific CAR	DMZSD3T	leukaemia	2A60-2B33	Phase 1	[33]
Retroviral vector-transduced autologous T cells to express CD22-specific CARs	DMZ8WAQ	Diffuse large B-cell lymphoma	2A81	Phase 1	[34]
TRPH-222	DMSLQW2	B-cell lymphoma	2A86	Phase 1	[35]
UCART-22	DMARHU4	B-cell acute lymphoblastic leukaemia	2B33.3	Phase 1	[36]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DCDT-2980S	DMGM2HY	Diffuse large B-cell lymphoma	2A81	Discontinued in Phase 2	[37]
RG7593	DM32IV4	Haematological malignancy	2B33.Y	Discontinued in Phase 2	[38]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ATA2431	DM34FEA	B-cell lymphoma	2A86	Preclinical	[39]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Anti-CD22/CD19 mab-toxin conjugate	DM8QIB2	Acute lymphoblastic leukaemia	2A85	Investigative	[40]
MEDI-553	DM960DQ	Autoimmune diabetes	5A10	Investigative	[41]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2C82	Bone marrow	1.89E-11	-0.21	-0.58

References

• [1] Safety and immunogenicity of recombinant Bacille Calmette-Gu |rin (rBCG) expressing Borrelia burgdorferi outer surface protein A (OspA) lipoprotein in adult volunteers: a candidate Lyme disease vaccine. Vaccine. 1999 Feb 26;17(7-8):904-14.
• [2] Results of inotuzumab ozogamicin, a CD22 monoclonal antibody, in refractory and relapsed acute lymphocytic leukemia. Cancer. 2013 Aug 1;119(15):2728-36.
• [3] Antibody fusion proteins: anti-CD22 recombinant immunotoxin moxetumomab pasudotox. Clin Cancer Res. 2011 Oct 15;17(20):6398-405.
• [4] New developments in immunosuppressive therapy for heart transplantation. Expert Opin Emerg Drugs. 2009 Mar;14(1):1-21.
• [5] Anti-CD22 immunotoxin RFB4(dsFv)-PE38 (BL22) for CD22-positive hematologic malignancies of childhood: preclinical studies and phase I clinical trial. Clin Cancer Res. 2010 Mar 15;16(6):1894-903.
• [6] ClinicalTrials.gov (NCT03312205) CAR-T Cells for Relapsed or Refractory Haematopoietic and Lymphoid Malignancies
• [7] ClinicalTrials.gov (NCT03125577) Combination CAR-T Cell Therapy Targeting Hematological Malignancies
• [8] ClinicalTrials.gov (NCT03098355) Interleukin-2 Following 4SCAR19/22 T Cells Targeting Refractory and/or Recurrent B Cell Malignancies
• [9] ClinicalTrials.gov (NCT03185494) Treatment of Relapsed and/or Chemotherapy Refractory B-cell Malignancy by Tandem CAR T Cells Targeting CD19 and CD22
• [10] ClinicalTrials.gov (NCT03121625) CAR-T Therapy in Relapsed or Refractory Haematopoietic and Lymphoid Malignancies
• [11] ClinicalTrials.gov (NCT03262298) Anti-CD22 CAR-T Cell Therapy Targeting B Cell Malignancies
• [12] ClinicalTrials.gov (NCT03289455) CD19 /22 CAR T Cells (AUTO3) for the Treatment of B Cell ALL
• [13] ClinicalTrials.gov (NCT03614858) CD19/CD22-targeted Chimeric Antigen Receptor Engineered T Cell (CART) in B-Cell Acute Lymphoblastic Leukemia.
• [14] ClinicalTrials.gov (NCT03468153) Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy for CD19+CD22+ Relapsed and Refractory Lymphoma
• [15] ClinicalTrials.gov (NCT02903810) Combination Transfer of CD19-TCRz-41BB and CD22-TCRz-41BB CAR-T Cells for B-cell Hematologic Malignancy
• [16] ClinicalTrials.gov (NCT02794961) CD22 Targeting CAR-T Therapy Against B Cell Hematological Malignancies
• [17] ClinicalTrials.gov (NCT02935153) A Clinical Research of CD22-Targeted CAR-T in B Cell Malignancies
• [18] 2011 Pipeline of Seattle Genetics.
• [19] ClinicalTrials.gov (NCT03291444) CAR-T Cells Combined With Peptide Specific Dendritic Cell in Relapsed/Refractory Leukemia/MDS
• [20] ClinicalTrials.gov (NCT02588456) Pilot Study of Autologous Anti-CD22 Chimeric Antigen Receptor Redirected T Cells In Patients With Chemotherapy Resistant Or Refractory Acute Lymphoblastic Leukemia
• [21] ClinicalTrials.gov (NCT02650414) CD22 Redirected Autologous T Cells for ALL
• [22] ClinicalTrials.gov (NCT03620058) CART22 Alone or in Combination With huCART19 for ALL
• [23] ClinicalTrials.gov (NCT03241940) CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Children or Young Adults With Recurrent or Refractory CD19 Positive B Acute Lymphoblastic Leukemia
• [24] ClinicalTrials.gov (NCT03448393) CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies
• [25] ClinicalTrials.gov (NCT03233854) CD19/CD22 Chimeric Antigen Receptor T Cells and Chemotherapy in Treating Patients With Recurrent or Refractory CD19 Positive Diffuse Large B-Cell Lymphoma or B Acute Lymphoblastic Leukemia
• [26] ClinicalTrials.gov (NCT03407859) Sequential Treatment With CD20/CD22/CD10-CART After CD19-CART Treatment Base on MRD in Relapsed/Refractory B-ALL
• [27] ClinicalTrials.gov (NCT03244306) A Phase 1 Study of CD22-CAR TCell Immunotherapy for CD22+ Leukemia and Lymphoma
• [28] A phase I study of a combination of anti-CD19 and anti-CD22 immunotoxins (Combotox) in adult patients with refractory B-lineage acute lymphoblastic leukaemia.Br J Haematol.2011 Aug;154(4):471-6.
• [29] ClinicalTrials.gov (NCT03463928) A Feasibility and Safety Study of Concomitant Therapy With Allo-CAR-T Cells and Allo-HSCT in Patients With Relapse or Refractory Leukemia
• [30] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [31] ClinicalTrials.gov (NCT04540796) A Phase 1, First-in-Human, Dose Escalation Study of the JNJ-75348780 Bispecific Antibody Targeting CD3 and CD22 in Participants With NHL and CLL. U.S.National Institutes of Health.
• [32] Clinical pipeline report, company report or official report of Innate Pharma.
• [33] ClinicalTrials.gov (NCT03330691) A Feasibility and Safety Study of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy for CD19+CD22+ Leukemia and Lymphoma
• [34] ClinicalTrials.gov (NCT02721407) Anti-CD22 CAR-T Therapy for CD19-refractory or Resistant Lymphoma Patients
• [35] Clinical pipeline report, company report or official report of Triphase Accelerator.
• [36] Clinical pipeline report, company report or official report of Cellectis.
• [37] Efficacy and toxicity of a CD22-targeted antibody-saporin conjugate in a xenograft model of non-Hodgkin's lymphoma. Oncoimmunology. 2012 December 1; 1(9): 1469-1475.
• [38] Clinical pipeline report, company report or official report of Roche.
• [39] Clinical pipeline report, company report or official report of Atara Biotherapeutics.
• [40] Immunotoxins against CD19 and CD22 are effective in killing precursor-B acute lymphoblastic leukemia cells in vitro. Leukemia. 2000 May;14(5):853-8.
• [41] 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: 2786).