Researchers from Roswell Park Comprehensive Cancer Center report that a new approach to immunotherapy could overcome some of the challenges of treating ovarian cancer by leveraging the power of endogenous (host) T cells using engineered T cells to deliver bispecific T-cell engagers, commonly referred to as BiTEs — a trademarked term for a type of fusion protein.

The research team believes this strategy could improve treatment outcomes in ovarian cancer, for which immunotherapy has been largely ineffective.

Findings from their preclinical study lay the groundwork for a new approach to targeting folate receptor alpha (FR⍺), an antigen commonly present in epithelial ovarian cancer and associated with advanced disease, chemotherapy resistance and disease relapse. 

The new study has been published in the Journal for ImmunoTherapy of Cancer.

The BiTE-secreting T-cell technology was developed in the laboratory of A J Robert McGray, PhD, principal investigator and first author of the study and Assistant Professor in the Department of Immunology at Roswell Park. 

Emese Zsiros, MD, PhD, FACOG, Chair of Roswell Park’s Department of Gynaecologic Oncology, was the study’s senior author.

The team’s findings suggest that this innovative therapy can have potent antitumour effects against ovarian cancer and holds promise for boosting immune responses in ovarian cancer patients.

Their approach involves a twist on conventional adoptive T-cell therapy (ACT), in which the patient’s own T cells are removed from the body and in some cases modified or engineered to recognise cancer cells.

The T cells are multiplied in the laboratory and then given back to the patient to mount an attack against the tumour.

ACT immunotherapy can result in complete and lasting therapeutic responses — no evidence of disease after treatment — for patients with other types of cancer, but so far it has been less successful against ovarian cancer. 

Previous research has shown that patients with ovarian cancer survive longer when their tumours have a robust accumulation of T cells.

However, many of those T cells appear to be “bystanders” — T cells that don’t recognise cancer cells or contribute to the antitumor immune response.

The research team’s new strategy of delivering T cells that secrete BiTEs results in not only activating the infused T cells but also redirecting the bystander T cells and increasing the overall attack on the tumour by T cells.  

The Roswell Park investigators built their strategy around FR⍺, a tumour antigen (or target) commonly found on ovarian cancer cells.

Using a technique called retroviral transduction, they created FR-B T cells, which secrete BiTEs that instruct T cells to home in on FR⍺-positive (FR⍺+) cancer cells. 

“We believe that FR-B T cells have the potential to generate potent antitumour immune responses against ovarian cancer and may, in the near future, benefit patients who otherwise are not expected respond to immunotherapy,” says Dr McGray.

“We are excited to continue developing this T-cell therapy and are working to advance this strategy to a clinical trial in patients with ovarian cancer.”

The investigators studied the antitumor effectiveness of FR-B T cells using tumour samples from ovarian cancer patients, FR⍺+ cancer cell lines, and preclinical tumour models.

They found that FR-B T cells:

• Efficiently destroyed FR⍺+ cell lines, targeted FR⍺+ ovarian cancer patient tumour cells, and rallied bystander T cells in the ovarian cancer tumour microenvironment by secreting T-cell engagers. 
• Could actively persist outside the tumour for prolonged periods of time, secreting BiTEs to redirect endogenous T cells present in the tumour to drive the tumour attack.  

Article: BiTE secretion by adoptively transferred stem-like T cells improves FRα+ ovarian cancer control

Source: Roswell Park Comprehensive Cancer Center