CRISPR CAR-T Insights | April

Posted on Apr 27, 2021

Airfinity, a science intelligence company, and CRISPR Medicine News have partnered to bring you a monthly newsletter on CRISPR CAR-T cells. Each month we will cover the important developments across conferences, press releases, news and publications.

Airfinity Overview 

CRISPR-Cas is being utilised in the context of chimeric antigen receptor (CAR)-T cells for immunotherapeutic applications, to overcome the existing short-comings around approved CAR-T candidates. 

CRISPR-Cas is used for gene knockouts or site-specific gene knock-ins. It is commonly used to generate allogenic “off-the-shelf” CAR-T cells (where cells are collected from healthy non-HLA matched donors) or to improve the potency of CAR-Ts. 

Candidate Overview

18 CRISPR edited CAR-T candidates are in clinical development for immuno-oncology applications. Most are anti-CD19 CAR-Ts for B-cell malignancies and utilise CRISPR to knockout TRAC, which is a mechanism to prevent immune reaction when cells are derived from healthy donors i.e. allogenic.

Conference Highlights 

The American Association for Cancer Research (AACR) 2021 virtual meeting kicked-off in April with week 1 featuring two CRISPR CAR-T relevant presentations from Gracell Biotechnology and CRISPR Therapeutics. 

Key takeaways include: 

  • GC027 (Gracell Biotechnology) presented encouraging data for R/R T-ALL patients supporting the use of their allogenic CAR-T candidate 

  • CRISPR Therapeutics shows CD70 KO in CAR-T cells improves function, supporting their CTX130 candidate in development

Gracell biotechnology’s TruUCAR enabled GC027 anti-CD7 CAR-T shows promising efficacy as standalone therapy in heavily pre-treated R/R T-ALL pts with a manageable safety profile

Candidate: GC027 | CRISPR modification: TRAC and CD70 KO | Company: Gracell Biotechnology | Presentation Type: Late Breaking ePoster 

Results from an ongoing phase 1 trial in patients with relapsed or refractory T-cell acute lymphoblastic leukaemia (r/r T-ALL):

  • 5 out of 6 patients given a single infusion of GC027 achieved minimum residual disease negative complete remission (MRD-CR) at month 1 

  • 3 out of 5 remained MRD-CR/CRi post 6 months (16.8, 9, 7 mo). 

  • The sample size of 6 is very small therefore further investigation is required to draw any complete conclusions. The trial is expected to complete in 2022. 

Safety: All patients developed cytokine release syndrome which was resolved after treatment. No neurotoxcity (ICANS) or acute graft-versus-host disease (aGvHD) seen. The latter is especially important as these are “off-the-shelf” CAR-T’s and therefore from non-HLA matched healthy donors and is achieved by the TRAC knock-out (KO).





CRISPR Therapeutics present encouraging preclinical data support CD70 knock-out to enhance T cell function

Candidate: CTX130 | CRISPR Modification: CD70 & β2M KO, CAR insertion to TRAC locus | Company: CRISPR Therapeutics | Presentation type: ePoster

CD70 CAR-T knock-out (KO) showed improved proliferation, the ability to enhance CAR-T’s targeting other antigens (CD-19, BCMA and CD33) and showed superior activity compared to other checkpoint KOs such as PD-1. 

These results support the CD70 KO CTX130 candidate which is currently phase I clinical trials for solid and heme malignancies. The company expect to report top-line data from these trials this year. 


Press Releases

Readouts for CRISPR Therapeutics’ CTX110, CTX120 and CTX130 expected later this year 

CRISPR therapeutics has 3 immuno-oncology candidates under development: CTX110, an anti-CD19 CAR-T for patients with relapsed or refractory B-cell malignancies, which reported positive top-line results late last year, CTX120, an anti-BMCA CAR-T for patients with relapsed or refractory multiple myeloma and CTX130, an anti-CD70 CAR-T for solid tumours and haematological malignancies. This year, CRISPR therapeutics expects to report additional data for CTX110 and top-line data from CTX120 and CTX130. 



EdiGene, which is developing a CRISPR edited U CAR-T for cancer applications, received approximately $67 million in a series B financing round

EdiGene’s research stage candidate, ET-02, is an allogenic CAR-T being developed for haematology, lymphoma and solid tumours with EdiGene’s partner, Immunochina who has expertise in CAR-T technology. The funding round was led by Loyal Valley Capital and the proceeds will be used to advance the company’s pipeline into clinical trials and scale business operations.


New Scientific Publications

Short-comings with off-target effects of CRISPR-Cas use for multiplex targeting in CAR-T cells, highlights the need for higher precision alternatives such as base-editing

In order for CAR-T immunotherapy to be more widely applied, allogenic CAR-Ts requiring multiple gene edits are needed to target refractory malignancies and solid tumours. Currently, CRISPR-Cas is the top choice for gene editing however off-target effects are a major short-coming. Base editing which facilitates single nucleotide alteration without double-stranded breaks or a DNA repair template, provide an attractive alternative to overcoming the off-target effects of CRISPR-Cas.


Nanjing Bioheng Biotech’s CTA101 universal CAR-T for r/r B-ALL showed prominent anti-leukaemic activity and a manageable safety profile  

Candidate: CTA101 | CRISPR Modification: CD52 & TRAC KO| Company: Nanjing Bioheng Biotech | Publication type: Peer reviewed article

In a phase 1 study using CTA101, a dual CD19/CD22 targeting CAR-T, 5 out of 6 patients achieved complete remission (CR) or CR with incomplete haematologic recovery (CR/CRi) at day 28 and 3 out of 5 remained CR/CRi and minimal residual disease (MRD) negative at a median follow-up of 4.3 months. Due to the small sample size of 6, further study is needed to confirm the efficacy of GC027. 

No neurotoxcity (ICANS), dose-limiting toxicity or acute graft-versus-host disease (aGvHD) seen. The latter is especially important as these are “off-the-shelf” CAR-T’s and therefore from non-HLA matched healthy donors. 


Looking Forward 

  • The American Association for Cancer Research (AACR2021) week 2 starts next month 17th May 

  • Quikin CD19-CART (Bioray Laboratories) is being investigated in patients with r/r B cell lymphoma in the trial NCT04213469 who’s primary completion date is set for next month, May 1st. 

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