New Hope for Cervical Cancer – A Promising Therapy


Cervical cancer, a major threat to women globally, is often linked to the human papillomavirus (HPV). While HPV vaccines effectively prevent the disease, treating established cancers remains a challenge. However, a recent breakthrough offers promising hope: rejuvenated cytotoxic T lymphocytes (rejTs) (Figure 1).

Figure 1: Graphical abstract.

These rejTs are immune cells specifically designed to target cancer. Ideally, they would be created from a patient’s own stem cells (iPSCs) for a personalised treatment. However, this approach is currently impractical.

Researchers have now achieved a significant feat: developing potent rejTs for cervical cancer treatment using allogeneic iPSCs. These are “standardised” iPSCs, not derived from each patient, but a crucial step toward wider applicability.

The challenge with allogeneic rejTs is rejection by the patient’s immune system. To address this, scientists employed a clever two-step gene editing approach using CRISPR-Cas9:

  1. Invisibility Cloak: HLA class I antigens, responsible for presenting “self” markers to the immune system, were deleted. This makes the rejTs invisible to CD8+ T cells that attack foreign cells.
  2. Selective Shield: Limited expression of specific HLA antigens (HLA-A24 and HLA-E) was introduced. This allows the rejTs to evade attacks from NK cells, which target cells lacking these surface proteins. Notably, HLA-A24 compatibility covers a significant global population.

These gene-edited rejTs displayed promising results:

  • They evaded detection and elimination by the immune system.
  • They effectively targeted and destroyed cervical cancer cells.

In mice with cervical cancer, rejT therapy led to:

  • Increased survival rates.
  • Significantly reduced tumor size and growth.

Further analysis revealed an added benefit: the rejTs included a high number of tissue-resident memory T cells. These cells reside in the cervix, offering potentially long-term protection against cancer recurrence.

This research presents a significant step forward in cervical cancer therapy. Gene-edited rejTs hold immense potential for a future where effective, personalized treatment options are widely available.

Journal article: Furukawa, Y., et al, 2023. iPSC-derived hypoimmunogenic tissue resident memory T cells mediate robust anti-tumor activity against cervical cancer, Cell Reports Medicine.

Summary by Stefan Botha

International Union of Immunological SocietiesUniversity of South AfricaInstitute of Infectious Disease and Molecular MedicineElizabeth Glazer Pediatric Aids Foundation