Cell therapy technology is changing rapidly, does CAR-T still have advantages?

In recent years, immunotherapy, as an emerging tumor treatment method, has become a hotspot in the research of malignant tumor treatment
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For hematological malignancies, the most popular treatment nowadays is CAR-T therapy

Up to now, there are 7 CAR-T products on the market worldwide, of which 2 are domestic, from Fosun Kate and WuXi Junuo Data source: Yaozhi Data

Although the high cost of CAR-T therapy is daunting, its breakthrough therapeutic effect also gives people hope and attracts many domestic and foreign companies to invest in it
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This year, the 63rd Annual Meeting of the American Society of Hematology (ASH) will be held in the United States from December 11th to 14th in the form of offline and online
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According to public information, many companies will announce the latest research results of their cell therapy products at the ASH annual meeting.

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Source: ASH

Second-line treatment of lymphoma, Gilead and BMS seize the opportunity

At present, various companies are working hard to promote CAR-T therapy to earlier tumor treatment
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Among them, Gilead’s Yescarta and Bristol-Myers Squibb’s Breyanzi have made the fastest progress

Previously, Bristol-Myers Squibb reported that TRANSFORM has reached its primary endpoint of EFS, as well as its secondary goals for complete response rate (CR) and progression-free survival (PFS)
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The top-line results of the ZUMA-7 trial of Yescarta for second-line treatment of patients with relapsed or refractory large B-cell lymphoma (LBCL) showed superiority compared with the current standard of care (SOC) for LBCL patients

It is also worth noting that Breyanzi was only approved for marketing in February this year for the treatment of adult patients with relapsed/refractory LBCL who have received two or more systemic treatments.
The proportion of CD4 positive T cells is controlled, which can better control the side effects of cell therapy; Breyanzi (lisocabtagene maraleucel) in the phase 3 clinical trial of the primary endpoint and key secondary endpoint results showed that compared with standard treatment, significantly improved Event-free survival, complete remission rate and progression-free survival of patients with relapsed/refractory large B-cell lymphoma (LBCL)
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However, Novartis is not so lucky
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In August of this year, Novartis announced that the CD19 CAR-T therapy Kymriah second-line treatment of aggressive B-cell non-Hodgkin lymphoma (B-NHL) Phase 3 clinical BELINDA did not meet the primary endpoint EFS

However, this year Novartis will announce the early clinical results of two other CAR-Ts, YTB323 targeting CD19 and PHE885 targeting BCMA
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A variety of domestic CAR-T will be unveiled at the ASH annual meeting

Johnson & Johnson/Legendary Biotech will present the CARTITUDE series of studies at the ASH Annual Meeting in 2021 (CAR-T therapy targeting BCMA-Cidacchi Olensay cilta-cel for the treatment of patients with relapsed or refractory multiple myeloma) Updated data
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In 2018, the product was approved by the IND in China and the United States, and one year later, it was approved as a breakthrough therapy by the FDA

In addition, Legend Bio will share the pre-clinical in vivo data of the new trispecific single domain antibody (VHH) CAR-T (LCAR-AIO) for the first time
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LCAR-AIO targets the three antigens of CD19, CD20 and CD22, and has the potential to be developed for the treatment of recurrent B-cell lymphoma and patients who have previously received CD19 CAR-T therapy

In addition to cilta-cel, Keji Bio's BCMA CAR-T and Genxi Bio's CD19/CD7 dual-targeting CAR-T will also appear at this year's ASH annual meeting
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Keji Pharmaceutical will publish the latest research data of CT053 in the form of a poster at this year's ASH annual meeting
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CT053 (zevorcabtagene autoleucel, abbreviated as Zevo-cel) is a fully human anti-autologous BCMA CAR-T cell candidate product independently developed by Keji Pharmaceutical.

Genxi Biotech will announce the preclinical research data of its CAR-T cell therapy candidate product GC502 for the treatment of B-cell malignant tumors at the conference in the form of an electronic poster
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GC502 is a CD19/CD7 dual-targeting, ready-to-use allogeneic CAR-T cell monotherapy
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Universal cell therapy on the stage

In addition to autologous CAR-T, more cutting-edge cell therapy solutions will be unveiled at this ASH annual meeting.
These new technologies may push cell therapy to the first-line hematoma treatment
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PBCAR0191 is a universal allogeneic CD19 targeted CAR-T cell therapy developed by Precision and Servier.
It is derived from qualified donor T cells and has undergone gene editing to remove the endogenous T cell receptor (TCR).
And inserting CAR into the same site
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PBCAR0191 is conducting a Phase 1/2a study to evaluate the safety and tolerability of PBCAR0191 in adult patients with R/R B-ALL and R/R non-Hodgkin’s lymphoma (NHL)
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Previously, FDA has granted PBCAR0191 treatment of mantle cell lymphoma (MCL) L of orphan status (the ODD)
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ALLO-501 is an anti-CD19 allogeneic CAR-T therapeutic drug developed by Allogene.
ALL-501 has achieved 75% ORR and 50% CR in the phase I trial of relapsed/refractory large B-cell lymphoma
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In addition, Fate's CAR-NK project FT596 has also attracted much attention
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FT596 is the first cellular immunotherapy product based on natural killer (NK) cells on sale, and also the first cellular immunotherapy product that has been genetically engineered to include three active anti-tumor ingredients
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At ASH 2019, Fate reported a preclinical study of FT596, which confirmed that cellular immunotherapy for B-cell tumors may eventually become a ready-made product that can be mass-produced uniformly
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More data will be released this year
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Companies such as Fate are also developing universal cell therapies based on iPSC cell differentiation
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In addition, multi-target cell therapy has also shown its advantages
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At present, we don't know much about cell therapy
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In the future, cell therapy will definitely be different .
Scientific development is endless, and the problems that currently plague us may be solved in the future, and "curing" blood tumors will also become a reality
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Reference source

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