Clinical Update: News on Two Cancer Gene Editing Trials

Iovance Biotherapeutics, a late-stage biotech company headquarted in California, announced last week that the U.S. FDA had cleared an IND appplication for IOV-4001, the company's first TALEN-edited cell therapy for unresectable or metastatic melanoma and stage III or IV non small cell lung cancer (NSCLC).

IND clearance from the FDA means that Iovance can now begin preparing for a clinical trial in the U.S., to evaluate IOV-4001 in patients with metastatic melanoma or stage III or IV NSCLC. The trial is expected to begin later this year.

IOV-4001 is a TALEN-edited tumour-infiltrating lymphocyte therapeutic candidate

IOV-4001 is developed using Cellectis' TALEN® gene-editing technology under licence. Specifically, it is generated from tumour-infiltrating lymphocytes that are isolated from patient tumours. TILs refer to a population of lymphocytes (including B cells, T cells, and other immune cell types) that naturally invade tumour tissue and are implicated in killing tumour cells. Following isolation, the TILs are subjected to TALEN gene editing to inactivate the PD-1 protein.

PD-1 is an immune checkpoint protein found on the surfaces of healthy T cells as well as certain cancer cell types. Under normal physiological conditions, the interaction between PD-1 and its ligand PD-L1 mediates T cell immune suppression, but cancer cells can hijack this pathway to escape the immune response. The PD-1/PD-L1 interaction is a well-established target for cancer immunotherapy and to date various small molecule and antibody-based inhibitors of both interaction partners have been pursued as cancer treatments.

IOV-4001 is designed as an adoptive cell therapy that combines the natural anti-tumour activity of TILs with PD-1 knockout to prevent immune escape by cancer cells, and according to the company's press release, IOV-4001 has the potential to become an optimised, next-generation TIL therapy for several solid tumour cancers.

We recently reported on a similar approach led by Özcan Met at a Danish Cancer Centre, using CRISPR-Cas9 to combine PD-1 knockout with adoptive TIL therapy for cancer. You can read that interview here.

Pre-clinical data for IOV-4001 to be presented in April 2022

Iovance Biotherapeutics will present a poster highlighting pre-clinical activity, details about the clinical-scale manufacturing process, and characterisation of IOV-4001 at the American Association for Cancer Research (AACR) 2022 Annual Meeting next month. The company reports in its AACR abstract that the anti-tumor activity of IOV-4001 was superior to non-edited TILs, as well as non-edited TILs in combination with an anti-PD-1 antibody, in a murine model for melanoma.

First patient dosed in Wugen's WU-CART-007 trial for blood cancers

Last week, Wugen Inc. announced that the first patient had been dosed in its Phase 1/2 trial for WU-CART-007 in relapsed or refractory (R/R) T-cell acute lymphoblastic leukaemia (T-ALL)/lymphoblastic lymphoma (LBL).

WU-CART-007 is an allogeneic CD7-targeting CAR-T cell therapy candidate developed using CRISPR-Cas9 technology. Specifically, the candidate is developed from healthy donor cells in which CD7 and the T-cell receptor alpha constant (TRAC) are disrupted via CRISPR-Cas9. TRAC disruption prevents CAR-T cell fratricide and mitigates the risk of graft-versus-host-disease (GvHD).

In the same press release, the company announced that the U.S. FDA had granted Orphan Drug Designation to WU-CART-007 for the treatment of ALL. Wugen presented pre-clinical data for WU-CART-007 supporting its safety and efficacy for T-cell malignancies at last year's Annual Society of Hematology (ASH) Annual Meeting.

We strive to bring you all the clinical updates for gene-edited therapies. For a complete overview of current gene-editing clinical therapeutic trials as well as diagnostic trials, check out CRISPR Medicine News' Clinical Trials Database.