Leronlimab Linked to Increased PD-L1 in Triple-Negative Breast Cancer

Leronlimab increased PD-L1 in patients with triple-negative breast cancer, potentially making cold tumors responsive to immune checkpoint inhibitors: © stock.adobe.com.

Leronlimab treatment was tied to an increased expression of an immune cell protein or “checkpoint inhibitor” known as programmed death-ligand 1 (“PD-L1”) on circulating tumor cells in patients with metastatic triple-negative breast cancer, according to a news release from CytoDyn Inc. In turn, this suggests a novel mechanism of action for leronlimab treatment in solid tumors.

Leronlimab is a CCR5 antagonist with the potential for multiple therapeutic indications.

CytoDyn reported that 15 of 17 patients (88%) who received weekly doses of 525 milligrams or more of leronlimab showed a significant rise in PD-L1 levels on circulating tumor cells within 30 to 90 days. This increase may help make tumors more responsive to immune checkpoint inhibitors by shifting them from “cold” to “hot” and potentially improving treatment outcomes.

According to the National Cancer Institute, cold tumors describe a tumor that does not trigger a strong immune response. These tumors are often surrounded by cells that block immune activity, preventing T-cells from attacking. Cold tumors usually resist immunotherapy.

Furthermore, hot tumors describe a tumor that triggers a strong immune response. These tumors often display surface markers that help T-cells recognize and attack them. Hot tumors are more likely to respond to immunotherapy.

“Leronlimab’s induction of PD-L1 on [circulating tumor cells] in patients with otherwise “cold” tumors opens a promising field of exploration for what could amount to significant improvements to patient care and outcomes in solid tumor oncology,” Dr. Richard Pestell, the company’s lead consultant in preclinical and clinical oncology, said in the news release. “We are hopeful that further short-term investigation will confirm our working theory and open new pathways for patients with a range of common and aggressive forms of cancer to access treatment options that were previously out of reach.”

In a small group of patients with metastatic triple-negative breast cancer who had previously received a median of two treatments, leronlimab was associated with improved overall survival, CytoDyn has previously announced. All five patients who showed a marked increase in PD-L1 expression after treatment and went on to receive an immune checkpoint inhibitor are still alive. Four have no evidence of disease, while the fifth is stable, as per the company.

If confirmed in future studies, this approach may offer a potential benefit to patients with solid tumors that have low PD-L1 levels and are not candidates for checkpoint inhibitors.

“We are thrilled to announce this apparent mechanism behind the improved survival in patients with refractory and metastatic [triple-negative breast cancer],” Dr. Jacob Lalezari, CEO of CytoDyn, said in the news release. “Leronlimab’s ability to induce an inflamed or “hot” tumor environment, that could then be treated with [immune checkpoint inhibitors], would be a game changer in solid tumor oncology. Prospectively confirming these findings in patients with [triple negative breast cancer] is a top priority. We have also amended our current colorectal cancer trial to ensure the prospective collection of PD-L1 data in a second type of solid tumor.”

What is Leronlimab and Triple-Negative Breast Cancer?

Leronlimab is an experimental humanized antibody designed to bind to CCR5, a protein on some immune cells involved in various diseases. It is being studied for cancer, infectious diseases and autoimmune conditions, as per the release.

As per the National Cancer Institute, triple-negative breast cancer is a type of breast cancer whose tumor cells lack estrogen receptors, progesterone receptors, and high levels of HER2/neu protein. Identifying this subtype is important for treatment decisions. It is also called ER-negative PR-negative HER2/neu-negative breast cancer or TNBC.

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