Overview of CD22-Targeted CAR Cell Therapies

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Backgrounds of CD22

CD22 is a B-cell surface molecule also known as Sialic acid-binding Ig-like lectin2 (Siglec-2). It regulates the activity and maturation of B cells mainly by interacting with sugar molecules on the cell surface. CD22 is a supramembrane glycoprotein with a full length of approximately 1350 amino acid residues. CD22 contains a short tail located on the cytoplasmic side and a large N-terminus located extracellularly. The N-terminus of CD22 is rich in Ig structural domains that can be used to bind to other proteins, including the Igα/Igβ subunit within the B-cell receptor (BCR) complex and CD22L, another Siglec family member on the natural killer (NK) cell receptor. These binding interactions can be mediated by regulating multiple key molecules in the B-cell signal transduction pathway. The intracellular tail of CD22 also contains several distinct structural domains, including a titin chain reaction sequence, a CTYC/CXXC-like zinc finger domain, and a Hormone Binding Domain (HBD). Among them, the titin chain reaction sequence and the CTYC/CXXC-like zinc finger domain function mainly to connect CD22 to the B-cell membrane and regulate its signaling pathways. Moreover, CD22 is associated with a variety of B-cell-related diseases, including acute lymphoblastic leukemia, non-Hodgkin's lymphoma, and multiple sclerosis in adults and children. Based on these findings, CD22 has emerged as a widely studied target for immunotherapy.

Fig.1 Structure of CD22

CD22 Signaling Pathways

CD22 is a negative regulator that binds to Igα/Igβ subunits, thereby inhibiting BCR signaling. In the inactivated state, CD22 inhibits BCR signaling by binding directly to Igα/Igβ subunits, thereby preventing the onset of autoimmune responses. In addition, CD22 can be dissociated by phosphorylation of key enzymes in the presence of activated BCR, thereby releasing the BCR signaling pathway.

The role of CD22 played in regulating the BCR signaling pathway is an important factor affecting B cell function. Several studies have shown that CD22 is associated with autoimmune diseases and malignant lymphomas. Also, phosphorylation modifications of key CD22 enzymes are abnormal. The expression of CD22 is significantly downregulated in some autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and autoimmune hemolytic anemia. All these abnormalities may lead to the loss of the original negative regulatory role of CD22, thereby compromising the regulatory BCR signaling pathway and leading to the development of autoimmune diseases.

The mechanism of action and expression of CD22 in B-cell lymphomas are complex. Some studies have found that the expression of CD22 is different in different types of B-cell lymphomas. CD22 also influences the development and prognosis of lymphoma by regulating the interaction of cell signaling pathways in the tumor microenvironment. The role of BCR signaling pathway in chronic lymphocytic leukemia indicates that BCR signaling pathway plays an important role in chronic lymphocytic leukemia, participating in the biological processes of leukemia cell proliferation, survival, invasion and so on. Therefore, inhibition of BCR signaling pathway is expected to be a new target for the treatment of chronic lymphocytic leukemia. In addition, studies have suggested the synergistic effect of CD22 and BCR signaling pathways in Hodgkin's lymphoma. CD22 and BCR signaling pathways have a synergistic effect in Hodgkin's lymphoma, influencing each other to affect the proliferation, survival and metastasis of tumor cells. Therefore, simultaneous targeting of CD22 and BCR signaling pathways may be one of the effective strategies for treating Hodgkin's lymphoma.

Clinic Status of CD22-Targeted CAR Cell Therapies

CD22 is widely used in CAR-T cell therapy as a target for the treatment of B-cell malignancies. The therapy uses modified T cells engineered to bind to specific antigen receptors to form CAR-T cells that enable them to recognize and attack excess B cells in the body. CAR-T cell therapy targeting CD22 has shown extremely high cure rates in clinical trials. CD22 There are currently a number of ongoing clinical trials in CAR-T cell therapy targeting CD22. Most of the CD22 CAR-T clinical trials are still in the early stages, including Phase I/II. CD22 CAR-T cell therapy is mainly used for the treatment of B-cell malignancies, such as acute lymphoblastic leukemia (ALL) and B-cell lymphoma. Most trials use autologous T cells or peripheral blood stem cells as the cell source. CD22 CAR-T cells can be used in combination with other target CAR-T cells to enhance the therapeutic effect. For example, in the treatment of B-cell malignancies, CD22 and CD19 are often expressed together, so the combination of CD22 and CD19 CAR-T cells can be used to improve the therapeutic effect.

Table 1. Ongoing CD22-Targeted CAR Cell Therapy Clinical Trials

NCT Number

Title

Status

Conditions

Sponsor/Collaborators

Phases

NCT04715217	Targeting CD19 and CD22 CAR-T Cells Immunotherapy in Patients With Relapsed or Refractory B Cell Lymphoma	Recruiting	Lymphoma, B-Cell	Shanxi Province Cancer Hospital\|Shanghai Ultra-T Immune Therapeutics Co. LTD	Phase 1\|Phase 2
NCT05507827	Safety of Myeloablative Conditioning, Orca-T, and Allogeneic, Donor-Derived CD19/CD22-CAR (Chimeric Antigen Receptor) T Cells in Adults With B-cell Acute Lymphoblastic Leukemia (ALL)	Recruiting	Lymphoid Leukemia	Crystal Mackall, MD\|Orca Biosystems, Inc.\|Stanford University	Phase 1
NCT04088890	Autologous CD22 CAR-T Cells in Adults w/ Recurrent or Refractory B Cell Malignancies	Recruiting	B-ALL\|B-cell Non Hodgkin Lymphoma\|DLBCL\|Follicular Lymphoma Grade 3B	Stanford University	Phase 1
NCT04788472	Sequential CD19 and CD22 CAR-T Therapy for Newly Diagnosed Ph+ B-ALL	Recruiting	B-Cell Acute Lymphoblastic Leukemia, Adult	Zhejiang University\|Yake Biotechnology Ltd.	Phase 1\|Phase 2
NCT04740203	Sequential CD19 and CD22 CAR-T Therapy for Newly Diagnosed Ph- B-ALL	Recruiting	B-Cell Acute Lymphoblastic Leukemia, Adult	Zhejiang University\|Yake Biotechnology Ltd.	Phase 1\|Phase 2
NCT04714593	Targeting CD19 and CD22 CAR-T Cells Immunotherapy in Patients With Relapsed or Refractory Acute B Lymphocytic Leukemia	Recruiting	Acute LAymphocytic Leukemia, B-Cell	Shanxi Province Cancer Hospital\|Shanghai Ultra-T Immune Therapeutics Co. LTD	Phase 1\|Phase 2
NCT04034446	CD19-CD22 Chimeric Antigen Receptor T (CAR-T) Cell for Treatment of B Cell Acute Lymphoblastic Leukemia (B-ALL)	Active, not recruiting	Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia	Institute of Hematology & Blood Diseases Hospital\|Juventas Cell Therapy Ltd.	Early Phase 1
NCT05418088	Genetically Engineered Cells (Anti-CD19/CD20/CD22 CAR T-cells) for the Treatment of Relapsed or Refractory Lymphoid Malignancies	Recruiting	Recurrent Acute Lymphoblastic Leukemia\|Recurrent B Acute Lymphoblastic Leukemia\|Recurrent B-Cell Prolymphocytic Leukemia\|Recurrent Chronic Lymphocytic Leukemia\|Recurrent High Grade B-Cell Lymphoma\|Recurrent Indolent Non-Hodgkin Lymphoma\|Recurrent Non-Hodgkin Lymphoma\|Recurrent Transformed Chronic Lymphocytic Leukemia\|Refractory Acute Lymphoblastic Leukemia\|Refractory B Acute Lymphoblastic Leukemia\|Refractory B-Cell Prolymphocytic Leukemia\|Refractory Chronic Lymphocytic Leukemia\|Refractory High Grade B-Cell Lymphoma\|Refractory Indolent Non-Hodgkin Lymphoma\|Refractory Non-Hodgkin Lymphoma\|Refractory Transformed Chronic Lymphocytic Leukemia	Sumithira Vasu\|Ohio State University Comprehensive Cancer Center	Phase 1
NCT05523661	Dasatinib Plus Anti-CD19/CD22 Bispecific CAR-T Cell Therapy for Elderly Ph-positive ALL Patients	Recruiting	Ph Positive ALL\|CAR-T Cell\|Dasatinib	Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine	Phase 1
NCT04499573	Bispecific CD19/CD22 CAR-T for Treatment of Children and Young Adults With r/r B-ALL	Active, not recruiting	B-ALL	Federal Research Institute of Pediatric Hematology, Oncology and Immunology	Phase 1\|Phase 2
NCT04556669	Anti-PD-L1 Armored Anti-CD22 CAR-T/CAR-TILs Targeting Patients With Solid Tumors	Recruiting	Solid Tumor, Adult\|Cervical Cancer\|Sarcoma\|NSCLC	Hebei Senlang Biotechnology Inc., Ltd.	Phase 1
NCT04029038	Modified Immune Cells (CD19-CD22 CAR-T Cells) in Treating Patients With Recurrent or Refractory CD19 Positive, CD22 Positive Leukemia or Lymphoma	Not yet recruiting	CD19 Positive\|CD22 Positive\|Minimal Residual Disease\|Progressive Disease\|Recurrent B Acute Lymphoblastic Leukemia\|Recurrent Chronic Lymphocytic Leukemia\|Recurrent Non-Hodgkin Lymphoma\|Refractory B Acute Lymphoblastic Leukemia\|Refractory Chronic Lymphocytic Leukemia\|Refractory Non-Hodgkin Lymphoma	M.D. Anderson Cancer Center\|National Cancer Institute (NCI)	Phase 1\|Phase 2
NCT02315612	Anti-CD22 Chimeric Receptor T Cells in Pediatric and Young Adults With Recurrent or Refractory CD22-expressing B Cell Malignancies	Recruiting	Follicular Lymphoma\|ALL\|NHL\|Large Cell Lymphoma	National Cancer Institute (NCI)\|National Institutes of Health Clinical Center (CC)	Phase 1
NCT03919526	Anti-CD19/CD22 Bispecific CAR-T Cell Therapy for MRD Positive ALL	Recruiting	MRD-positive\|Acute Lymphoblastic Leukemia	Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine	Phase 1
NCT03244306	A Phase 1 Study of CD22-CAR TCell Immunotherapy for CD22+ Leukemia and Lymphoma	Active, not recruiting	Leukemia	Seattle Children's Hospital	Phase 1
NCT03330691	A Feasibility and Safety Study of Dual Specificity CD19 and CD22 CAR-T Cell Immunotherapy for CD19+CD22+ Leukemia	Recruiting	Leukemia\|Lymphoma	Seattle Children's Hospital	Phase 1
NCT05674175	Co-administration of CART22-65s and huCART19 for B-ALL	Recruiting	B-cell Acute Lymphoblastic Leukemia\|B Lineage Lymphoblastic Lymphoma	Stephan Grupp MD PhD\|University of Pennsylvania\|Children's Hospital of Philadelphia	Phase 1\|Phase 2
NCT04340167	Study of Anti-CD22 CAR-T Cells Treating Leukemia Children	Recruiting	Acute Lymphoblastic Leukemia\|Acute Lymphoblastic Leukemia, in Relapse\|Refractory Acute Lymphoblastic Leukemia	Beijing Boren Hospital	Phase 2
NCT03241940	Phase I Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory B Cell Malignancies	Recruiting	B Acute Lymphoblastic Leukemia\|CD19 Positive\|Minimal Residual Disease\|Philadelphia Chromosome Positive\|Recurrent Adult Acute Lymphoblastic Leukemia\|Recurrent Childhood Acute Lymphoblastic Leukemia\|Refractory Acute Lymphoblastic Leukemia	Crystal Mackall, MD\|Stanford University	Phase 1
NCT05223686	To Evaluate the Safety and Tolerability of Human CD19-CD22 Targeted T Cells Injection for Subjects With R/R B-ALL.	Not yet recruiting	Acute Lymphoblastic Leukemia	Hrain Biotechnology Co., Ltd.\|Ruijin Hospital	Phase 1
NCT03233854	CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells With or Without NKTR-255 in Adults With Recurrent or Refractory B Cell Malignancies	Recruiting	B Acute Lymphoblastic Leukemia\|CD19 Positive\|Minimal Residual Disease\|Philadelphia Chromosome Positive	Crystal Mackall, MD\|California Institute for Regenerative Medicine (CIRM)\|Stanford University	Phase 1
NCT03448393	CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies	Recruiting	Acute Lymphoid Leukemia\|B-Cell Leukemia\|Leukemia, Lymphocytic, B Cell\|B-Cell Lymphoma\|Lymphoma, Non-Hodgkin	National Cancer Institute (NCI)\|National Institutes of Health Clinical Center (CC)	Phase 1
NCT05651178	Human CD19-CD22 Targeted T Cells Injection for Refractory/Relapsed Central Nervous System Leukemia/Lymphoma Patients	Recruiting	Central Nervous System Lymphoma	Hrain Biotechnology Co., Ltd.\|Second Affiliated Hospital of Nanchang University	Early Phase 1
NCT05442515	CD19/CD22 Bicistronic Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies	Recruiting	Acute Lymphoid Leukemia\|B-Cell Leukemia\|Leukemia, Lymphocytic, B Cell\|B-Cell Lymphoma\|Lymphoma, Non-Hodgkin	National Cancer Institute (NCI)\|National Institutes of Health Clinical Center (CC)	Phase 1\|Phase 2
NCT04648475	Safety and Efficacy of CD19 and CD22 Targeted CAR-T Therapy for Relapsed/Refractory B Cell Leukemia and Lymphoma	Recruiting	Leukemia, B-cell\|Lymphoma, B-Cell	Chongqing Precision Biotech Co., Ltd	Phase 1\|Phase 2
NCT05225831	Safety and Efficacy of CD19/CD22 Dual Targeted CAR-T Cell Therapy in R/R B-Cell Acute Lymphoblastic Leukemia	Recruiting	CD19+ and CD 22+ B-ALL	Hebei Senlang Biotechnology Inc., Ltd.\|Hebei Yanda Ludaopei Hospital	Early Phase 1
NCT04714827	Targeting CD19 and BCMA CAR-T Cells Immunotherapy in Patients With Relapsed or Refractory Multiple Myeloma	Recruiting	Multiple Myeloma	Shanxi Province Cancer Hospital\|Shanghai Ultra-T Immune Therapeutics Co. LTD	Phase 1\|Phase 2
NCT05094206	CAR20.19.22 T-cells in Relapsed, Refractory B-cell Malignancies	Recruiting	B-cell Non Hodgkin Lymphoma\|B-cell Chronic Lymphocytic Leukemia	Medical College of Wisconsin\|Miltenyi Biomedicine GmbH	Phase 1
NCT04815356	Phase I Study of Anti-CD22 Chimeric Receptor T Cells in Patients With Relapsed/Refractory Hairy Cell Leukemia and Variant	Recruiting	Hairy Cell Leukemia\|Hairy Cell Leukemia Variant	National Cancer Institute (NCI)\|National Institutes of Health Clinical Center (CC)	Phase 1
NCT05651100	Safety and Efficacy of Sequential CD19 and CD22 Targeted CAR-T Therapy for Relapsed/Refractory B Cell Lymphoma	Not yet recruiting	Lymphoma, B-Cell	Kecellitics Biotech Company Ltd\|Hebei Yanda Ludaopei Hospital	Phase 1\|Phase 2
NCT04303247	CD19 and CD22 Dual-targeted CAR-T Cells for Relapsed or Refractory B-NHL	Not yet recruiting	B-cell Lymphoma Refractory\|B-cell Lymphoma Recurrent	Xinqiao Hospital of Chongqing\|Gracell Biotechnology Shanghai Co., Ltd.\|920th Hospital of Joint Logistics Support Force of People's Liberation Army of China\|The Affiliated Hospital Of Guizhou Medical University\|Tang-Du Hospital\|The General Hospital of Western Theater Command\|Chongqing University Cancer Hospital	Early Phase 1
NCT04626739	CAR-T Cells in Treating Patients With Relapsed or Refractory NHL	Recruiting	Refractory Indolent Adult Non-Hodgkin Lymphoma	Hebei Senlang Biotechnology Inc., Ltd.	Early Phase 1
NCT04626726	Adult B-ALL Treated by CAR-T Cell Bridging Allogeneic Hematopoietic Stem Cell Transplantation	Recruiting	Adult B Acute Lymphoblastic Leukemia	Hebei Senlang Biotechnology Inc., Ltd.	Early Phase 1
NCT05388695	To Observe the Dual-target Chimeric Antigen Receptor T Cells in the Treatment of B Cell Hematologic Tumors	Recruiting	19 and 22+ B Cell Hematologic Tumors\|19 and 20+ B Cell Hematologic Tumors	Hebei Senlang Biotechnology Inc., Ltd.\|Tongji Hospital	Phase 1
NCT04601181	Safety and Efficacy of ThisCART22 in Patients With Refractory or Relapsed B Cell Malignancies	Recruiting	B Cell Malignancy	Fundamenta Therapeutics, Ltd.\|The First Affiliated Hospital of USTC (Anhui Provincial Hospital)	Phase 1
NCT05106946	Safety and Clinical Activity of ThisCART22 in Patients With r/r Non-Hodgkin's B Cell Lymphoma	Recruiting	B-cell Malignancy	Fundamenta Therapeutics, Ltd.\|The Affiliated Hospital of Xuzhou Medical University	Phase 1
NCT04626765	CAR-T for Children With Relapsed and Refractory Acute Lymphoblastic Leukemia	Recruiting	Childhood Acute Lymphoblastic Leukemia	Hebei Senlang Biotechnology Inc., Ltd.\|The Second Hospital of Hebei Medical University	Early Phase 1
NCT04340154	Study of Sequential CAR-T Cell Treating Leukemia Children	Recruiting	Acute Lymphoblastic Leukemia\|Acute Lymphoblastic Leukemia, in Relapse\|Refractory Acute Lymphoid Leukemia	Beijing Boren Hospital	Phase 2
NCT05206071	Clinical Study of SL19+22 CAR-T Cells for Relapsed or Refractory Non-Hodgkin Lymphoma	Recruiting	Non-hodgkin's Lymphoma	Hebei Senlang Biotechnology Inc., Ltd.	Not Applicable
NCT04283006	A Study of CD20/CD22 Targeted CAR T-cell Therapy for Relapsed or Refractory Lymphoid Malignancies	Recruiting	Relapsed and Refractory\|Lymphoid Hematological Malignancies	He Huang\|Yake Biotechnology Ltd.\|Zhejiang University	Early Phase 1
NCT04781634	a Clinical Research of CD19 and CD22 Targeted Prime CAR-T Cell in Relapsed/Refractory B-ALL	Recruiting	B-ALL	Chongqing Precision Biotech Co., Ltd	Phase 1\|Phase 2
NCT04782193	a Clinical Research of CD19 and CD22 Targeted Prime CAR-T Cell in Relapsed/Refractory B Cell Lymphoma	Recruiting	B Cell Lymphoma	Chongqing Precision Biotech Co., Ltd	Phase 1\|Phase 2
NCT05470777	CD22/CD19 CAR-T and Auto-HSCT Sandwich Strategy as Consolidation Therapy for B-ALL	Recruiting	B-cell Acute Lymphoblastic Leukemia	The First Affiliated Hospital of Soochow University\|National Natural Science Foundation of China(Grant No. 81970138)\|Jiangsu Province Natural Science Foundation of China (Grant No. BK20210091)\|Jining Medical University\|The Second People's Hospital of Huai'an\|First Affiliated Hospital Bengbu Medical College\|Northern Jiangsu Province People's Hospital\|Affiliated Hospital of Nantong University\|Suzhou Hospital of Traditional Chinese Medicine	Phase 1\|Phase 2
NCT04571138	A Pediatric and Young Adult Trial of Genetically Modified T Cells Directed Against CD22 for Relapsed/Refractory Leukemia or Lymphoma	Recruiting	Leukemia\|Lymphoma	Seattle Children's Hospital	Phase 1\|Phase 2
NCT04626908	Clinical Study of Targeting CD19 and CD22 Chimeric Antigen Receptor T Lymphocytes in the Treatment of Recurrent or Refractory B Cell Non-Hodgkin Lymphoma	Not yet recruiting	Relapsed and Refractory\|Lymphoid Hematological Malignancies	He Huang\|Gracell Biotechnology Ltd.\|Zhejiang University	Phase 1\|Phase 2
NCT02443831	CARPALL: Immunotherapy With CD19/22 CAR T-cells for CD19+ Haematological Malignancies	Active, not recruiting	Acute Lymphoblastic Leukemia\|Burkitt Lymphoma	University College, London	Phase 1
NCT05429905	Dual Anti-CD22/CD19 Chimeric Antigen Receptor-directed T Cells (CART2219.1) for Relapsed Refractory B-Lineage Leukaemia	Recruiting	Lymphoblastic Leukemia\|Lymphoblastic Leukemia, Acute, Childhood\|Lymphoblastic Leukemia in Children\|Lymphoblastic Leukemia, Acute Adult\|CAR	KK Women's and Children's Hospital\|Singapore General Hospital\|National University Hospital, Singapore	Phase 1\|Phase 2
NCT04204161	A Clinical Study of CAR-T Cells Treatment for Children With CD19+/CD22+ R/R ALL and Lymphoma	Recruiting	Relapsed B-cell Acute Lymphoblastic Leukemia, Childhood\|Refractory B-cell Acute Lymphoblastic Leukemia, Childhood\|Relapsed/Refractory B-cell Lymphoma, Childhood	Shenzhen BinDeBio Ltd.\|Xiangya Hospital of Central South University	Phase 1
NCT05098613	Preliminary Safety and Tolerability of CD19x22 CAR-T Cells in Adolescent and Adult R/R B-NHL Patients	Recruiting	Non-Hodgkin Lymphoma	University of Colorado, Denver	Phase 1
NCT03287817	CD19/22 CAR-T Cells (AUTO3) for the Treatment of Diffuse Large B Cell Lymphoma	Active, not recruiting	Diffuse Large B Cell Lymphoma\|Relapsed Diffuse Large B-Cell Lymphoma\|Refractory Diffuse Large B-Cell Lymphoma\|DLBCL	Autolus Limited	Phase 1\|Phase 2
NCT05091541	A Phase 1/2 Study of CT120 in Patient With Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma	Not yet recruiting	B-cell Non-Hodgkin's Lymphoma	Nanjing IASO Biotherapeutics Co., Ltd	Phase 1\|Phase 2
NCT04430530	4SCAR-T Therapy Post CD19-targeted Immunotherapy	Recruiting	CD19 Negative B-cell Malignancies	Shenzhen Geno-Immune Medical Institute\|ShiJiaZhuang Zhongxi Children Hospital\|Shenzhen Children's Hospital\|The Seventh Affiliated Hospital of Sun Yat-sen University	Phase 1\|Phase 2
NCT04429438	Multi-CAR-T Cells Targeting B Cell Lymphomas	Recruiting	B Cell Lymphoma (BCL)	Shenzhen Geno-Immune Medical Institute\|The Seventh Affiliated Hospital of Sun Yat-sen University\|Shenzhen Children's Hospital	Phase 1\|Phase 2
NCT04016129	CAR-T Immunotherapy Targeting CD19- ALL	Recruiting	B-cell Leukemia	Shenzhen Geno-Immune Medical Institute	Phase 1\|Phase 2
NCT03407859	Sequential Treatment With CD20/CD22/CD10-CART After CD19-CART Treatment Base on MRD in Relapsed/Refractory B-ALL	Recruiting	Therapy Related Leukemia	Zhujiang Hospital\|Nanfang Hospital of Southern Medical University	Early Phase 1
NCT05432882	CD19/22 Bi-specific CAR-T Cell Therapy	Recruiting	B Cell Malignancies	Shenzhen Geno-Immune Medical Institute	Phase 1\|Phase 2
NCT05010564	CAR-T Cell, B-cell Acute Lymphoblastic Leukemia (TriCAR)	Not yet recruiting	Leukemia, B-Cell	Baylor College of Medicine\|Texas Children's Cancer Center	Phase 1
NCT03614858	CD19/CD22-targeted Chimeric Antigen Receptor Engineered T Cell (CART) in B-Cell Acute Lymphoblastic Leukemia.	Recruiting	Leukemia, B-cell	Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd\|The First Affiliated Hospital of Soochow University	Phase 1\|Phase 2
NCT02650414	CD22 Redirected Autologous T Cells for ALL	Recruiting	B Cell Leukemias\|B Cell Lymphomas	University of Pennsylvania\|Children's Hospital of Philadelphia	Phase 1
NCT04150497	Phase 1/2 Study of UCART22 in Patients With Relapsed or Refractory CD22+ B-cell Acute Lymphoblastic Leukemia (BALLI-01)	Recruiting	B-cell Acute Lymphoblastic Leukemia	Cellectis S.A.	Phase 1
NCT05292898	A Triple-targeted Cell Preparation Targeting CD19/CD20/CD22 in Patients With Relapsed/Refractory B-cell Acute Lymphocytic Leukemia	Recruiting	Acute Lymphocytic Leukemia	Institute of Hematology & Blood Diseases Hospital\|Nanjing Legend Biotech Co.	Phase 1
NCT03620058	CART22 Alone or in Combination With huCART19 for ALL	Active, not recruiting	Chemotherapy Resistant Acute Lymphoblastic Leukemia\|Refractory Acute Lymphoblastic Leukemia	University of Pennsylvania	Phase 1
NCT05318963	Targeting CD19/CD20/CD22 Triple-targeted Cell in Patients With Relapsed/Refractory B-cell Lymphoma	Recruiting	B-cell Lymphoma Recurrent\|B-cell Lymphoma Refractory	Qiu Lugui\|Nanjing Legend Biotech Co.\|Institute of Hematology & Blood Diseases Hospital	Phase 1

References

Ereño-Orbea, June, et al. "Molecular basis of human CD22 function and therapeutic targeting." Nature communications 8.1 (2017): 764.
Pluvinage, John V., et al. "CD22 blockade restores homeostatic microglial phagocytosis in ageing brains." Nature 568.7751 (2019): 187-192.
CAR Linker Length Modulates CD22-Targeted CAR T-cell Efficacy in ALL. Cancer Discov. 2021;11 (7):1611.
Spiegel, Jay Y., et al. "CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial." Nature medicine 27.8 (2021): 1419-1431.