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Notification report


Full notification file


General information

Notification Number
B/NL/20/013

Member State to which the notification was sent
Netherlands

Date of acknowledgement from the Member State Competent Authority
20/07/2020

Title of the Project
Clinical study CRSP-ONC-003 titled: “A Phase 1, Open-Label, Multicenter, Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of Allogeneic CRISPR-Cas9–Engineered T Cells (CTX130) in Adult Subjects with Advanced, Relapsed or Refractory Renal Cell Carcinoma (RCC) with Clear Cell Differentiation”
Clinical study CRSP-ONC-004 titled: “A Phase 1, Open-Label, Multicenter, Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of Anti-CD70 Allogeneic CRISPR-Cas9-Engineered T Cells (CTX130) in Adult Subjects With Relapsed or Refractory T or B Cell Malignancies”


Proposed period of release:
01/10/2020 to 31/12/2025

Name of the Institute(s) or Company(ies)
Nederlands Kanker Instituut, Antoni van Leeuwenhoek ziekenhuis;


3. Is the same GMO release planned elsewhere in the Community?
No

Has the same GMO been notified elsewhere by the same notifier?
No

GMO characterization

GMO is a:
Other: mammals

Identity of the GMO:
The GMO (CTX130) consists of human allogeneic T cells that are genetically modified ex vivo using CRISPR/Cas9 gene editing components and a recombinant adeno-associated viral (rAAV) vector. The drug product is prepared from healthy donor peripheral blood mononuclear cells (PBMCs) obtained via a standard leukapheresis procedure. The mononuclear cells are enriched for T cells and activated with anti-CD3/CD28 antibody-coated beads, then electroporated with CRISPR/Cas9 ribonucleoprotein complexes, and transduced with a CAR gene–containing recombinant adeno-associated virus (AAV) vector. The modified T cells are expanded in cell culture, purified, formulated into a suspension, and cryopreserved. The product will be stored onsite and thawed immediately prior to administration.

The genetic modifications include disruption of the T cell receptor alpha constant (TRAC), β2-microglobulin (B2M), and CD70 loci and a simultaneous insertion of an anti-CD70 chimeric antigen receptor (CAR) transgene into the TRAC locus. The CAR is comprised of a humanized single-chain variable fragment (scFv) specific for CD70, followed by a CD8 hinge and transmembrane region that is fused to the intracellular signaling domain for CD137 (4-1BB) and CD3ζ. The TRAC and B2M disruptions reduce the probability of GvHD and rejection of CTX130, respectively, the CD70 disruption increases the health and activity of CTX130. The CAR insertion allows for specific targeting of CD70-expressing human tumors.


Information relating to the recipient or parental organisms from wich the GMO is derived
Common NameGenusSpeciesSubspeciesStrainPathovar
HumanHomoSapiens---

European Commission administrative information

Consent given by the Member State Competent Authority:
Yes
09/11/2020 00:00:00
Remarks: