The overall response rate was 96%, and Mustang Bio announced the latest clinical data on CD20 CAR-T therapy

April 27, 2022/eMedClub News/--On April 25, 2022, Mustang Bio (Mustang Bio) announced the interim data of the ongoing Phase 1/2 clinical trial of MB-106, which is An autologous CAR-T cell therapy targeting CD20, co-developed by Mustang and Fred Hutchinson Cancer Center (Fred Hutch), for the treatment of relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) and chronic Lymphocytic leukemia (CLL)
.

These data were presented by Fred Hutch and Mazyar Shadman, PhD, associate professor and physician at the University of Washington, at the Joint ASTCT and CIBMTR Transplantation and Cell Therapy Conference
.

 The study demonstrated high efficacy and a very good safety profile in all patients (n=25)
.

Five dose levels were used in the study, and complete remission was observed at all dose levels
.

Durable responses have been observed in a variety of hematological malignancies, including follicular lymphoma (FL), CLL, diffuse large B-cell lymphoma (DLBCL), and Waldenstrom's macroglobulinemia (WM)
.

Across all patients at all dose levels, an overall response rate (ORR) of 96% and a complete response rate (CR) of 72% were observed
.

In addition, two patients who had previously received CD19-targeted CAR-T therapy and subsequently relapsed, both responded to the treatment, with one FL patient achieving a CR and the other DLBCL patient achieving a partial response (PR)
.

 CAR-T expansion was observed at all dose levels
.

A favorable safety profile was observed in all 25 patients at the 28-day assessment
.

No patients developed grade 3 or 4 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS), and none of the FL patients (n=18) developed ICANS of any grade
.

 Dr.
Shadman said: "We are pleased that in this study, we observed a favorable safety profile and high rates of complete and durable remission
.

In addition, the response of patients who had previously received CD19-targeted CAR-T therapy showed that MB-106 acts as a Potential for immunotherapy options for these patients
.

This study is open to CD20+ B-NHL and CLL patients, including those who have received CAR-T therapy
.

" CAR-T therapy targeting CD20 CD20 is a human B-lymphocyte-restricted Sexual differentiation antigen, encoded by the MS4A1 gene (located at 11q12), is a hydrophobic 4-time transmembrane protein with a molecular weight of about 35kD.
Membrane 4 domain subfamily A member 1 et al
.

The protein function may be involved in the regulation of B cell activation and proliferation, possibly functioning as a calcium channel
.

  ▲ Expression of CD markers in different developmental stages of B lymphocytes (Image source: Science Direct) CD20 antigen mainly exists on pre-B and mature B lymphocytes, and is expressed on most B-cell non-Hodgkin's lymphoma cells, but not on In stem cells, primary B cells, normal plasma cells, or other normal tissues
.

Plasma cell naive cells and stimulated plasma cells may express CD20
.

 According to the expression characteristics of CD20 in the developmental stage of B lymphocytes, it has been selected as one of the targets for the treatment of B-cell lymphoma and leukemia
.

Therefore, more and more projects are developing CAR-T cell therapy based on this target
.

 On April 19, 2022, Adicet Bio announced that the U.
S.
FDA has granted Fast Track designation to its CD20-targeting allogeneic CAR-γδ T product candidate, ADI-001, for the treatment of relapsed or refractory B-cell non-Hodgkin lymphoma tumor (NHL)
.

Interim data from Phase 1 clinical study of ADI-001 in NHL showed that 3 out of 4 evaluable patients achieved remission, including 2 CR and 1 PR, no dose-limiting toxicity, graft-versus-host disease, ICANN or CRS level 3 or higher
.

Recommended reading: Universal CD20 CAR-γδ T cell therapy has been granted Fast Track designation by the US FDA.
What are the advantages of γδ T cells? On September 16, 2019, Precision BioSciences announced that the U.
S.
FDA has accepted a clinical trial application for the gene-edited allogeneic anti-CD20 CAR-T cell therapy PBCAR20A
.

PBCAR20A is being developed for the treatment of NHL, CLL and small lymphocytic lymphoma (SLL)
.

Recommended reading: Precision's gene-edited allogeneic CD20 CAR-T therapy has been approved for clinical useYimai Meng broke the
news
 As early as the end of 2012, the Molecular Immunity Department/Biotherapy Ward of the Chinese People's Liberation Army General Hospital carried out a clinical trial study of CD20-targeted CAR-T cells in the treatment of DLBCL internationally, and completed in 2014 and reported 7 cases for the first time.
The results of a phase I clinical study in patients showed that CD20 CAR-T cells combined with a cytoreductive conditioning regimen could prolong tumor regression
.

At the same time, the team also applied to the State Intellectual Property Office for a CD20 CAR-NKT patent (engineered CD20-targeted NKT cells and their preparation method and application, patent application number: 201410062069.
7)
.

 On January 22, 2021, the official website of the Center for Drug Evaluation (CDE) of the State Food and Drug Administration showed that Shanghai Longyao Biotechnology Co.
, Ltd.
's CD20 CAR-T cell therapy "LY007 cell injection" new drug clinical trial application obtained implied license ( Acceptance number: CXSL2000315), the indication is relapsed/refractory CD20 positive B-NHL, including: DLBCL and transformed follicular lymphoma (TFL)
.

It is worth mentioning that LY007 cell injection is the first CAR-T product targeting CD20 that has obtained clinical approval in China
.

 Recommended reading: China's first CD20 CAR-T cell obtains implied clinical licenseYimai Meng broke the news In addition, Sibeman has also developed CD19/CD20 dual-targeted CAR-T cell therapy C-CAR039, January 11, 2022 The US FDA granted C-CAR039 Regenerative Medicine Advanced Therapy (RMAT) and Fast Track (FT) designation for the treatment of relapsed or refractory and diffuse large B-cell lymphoma (r/r DLBCL)
.

C-CAR039 can simultaneously act on the dual targets of CD19 and CD20, and can effectively eliminate CD19/CD20 single-positive or double-positive tumor cells in vivo and in vitro
.

Early clinical results from an investigator-initiated clinical study (IIT) currently underway in China demonstrate the encouraging efficacy and favorable safety profile of C-CAR039
.

 Recommended reading: SIBIMAN’s CD19/CD20 CAR-T cell therapy has been granted dual qualifications by FDA for RMAT and Fast Track Reference: https:// phase-1-2-data-for-mb-106-cd20-targeted-car-t-therapy-in-patients-with-relapsed-or-refractory-b-cell-non-hodgkin-lymphoma-and-chronic- lymphocytic-leukemia/——List of recent popular events——▼April 27, Agilent Cell and Gene Therapy Webinar Series▼April 28, Focus on mRNA Industrialization: Key Considerations for Raw Materials and Purification Processes