Key research initiatives

Genetic modifications

  • Cellectis TALEN® collaboration agreement to support a clinical program
  • Genetically modified knockout TIL, with both single- and double- knockouts
  • IOV-4001 Investigational New Drug (IND) application
  • Additional immune checkpoint inhibitor (ICI) targets
  • Cytokine-tethered TIL
  • Additional transient and stable gene insertion and inactivation

Leveraging the gene-editing TALEN® platform licensed from the clinical-stage biotechnology company Cellectis, we are pursuing several targets for genetic modification. These include single- and double- knockout programs to further harness the immune system response to cancer and potentially increase the efficiency, potency and application of TIL therapy. Additional transient and permanent genetic modifications of TIL, such as cytokine-tethered TIL, may expand and activate TIL to achieve better efficacy while avoiding systemic side effects of cytokines. We are also developing additional TIL-cell lines using transient and stable gene insertion and inactivation.

IOV-4001 is our lead genetically modified TIL program. It uses the pioneering gene-editing TALEN® technology licensed from Cellectis to inactivate the gene coding for the programmed cell death protein-1 (PD-1), and develop next-generation therapies.

PD-1 is a checkpoint protein found on T cells that normally acts as an “off switch” to help to prevent T cells from attacking other cells in the body. It works by binding to PD-L1, a protein found on both normal and cancerous cells, thereby shutting down an attack by a T cell. By removal of this important barrier for T cells to attack cancer, IOV-4001 has the potential to become an optimized, next-generation TIL therapy for several solid tumor cancers.

We believe that IOV-4001 may provide important proof of concept for genetically modified TIL therapy incorporating the TALEN® technology.

Potency

  • PD-1+ selected TIL
  • CD39/69 double-negative TIL

Potential approaches to increase TIL potency include the sorting and selection of specific TIL, such as PD-1+ selected TIL, for the final TIL product. Under a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health (NIH) and the National Cancer Institute (NCI), we are also exploring selection of CD39/69 double-negative cells and the use of certain inhibitors or other reagents in TIL expansion cultures to enhance potency.

PD-1 is a checkpoint protein found on T cells that acts as an “off switch” to help to prevent T cells from attacking other cells in the body. It works by binding to PD-L1, a protein found on both normal and cancerous cells, thereby shutting down an attack by a T cell. 

Process optimization

  • Gen 3 (16-day) manufacturing process (COM-202)
  • Core biopsy (LUN-202 trial)

We are committed to further optimizing and streamlining the processes for collecting tumor samples and manufacturing TIL therapy. These efforts include our 16-day Gen 3 manufacturing process, which we are investigating in several patient cohorts in our clinical trials. We are also using our Gen 3 process to manufacture TIL from core biopsy as a less-invasive collection of tumor samples. Gen 3 with core biopsy is being explored in a cohort of patients with non-small cell lung cancer (NSCLC) in our IOV-LUN-202 trial.

New treatment regimens

  • IOV-3001 interleukin-2 (IL-2) analog licensed from Novartis: Investigational new drug (IND) enabling studies in 2022

We are investigating a novel IL-2 analog, IOV-3001, licensed from Novartis, in IND-enabling studies. We are developing IOV-3001 to administer after TIL therapy, to potentially become part of the TIL treatment regimen.

New tumor types

  • Explore potential for TIL therapy in other tumor types and treatment settings

Through our development of next-generation TIL, as well as our ongoing academic collaborations with leading cancer research centers and government and corporate partners, we are exploring the potential for TIL therapy in other oncology tumor types and treatment settings.

View Our Clinical Pipeline

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