iPSC-derived dendritic cells can work synergistically with radiation therapy to control both local and distant tumors
BUFFALO, N.Y. — A research team led by Fumito Ito, MD, PhD, FACS, of Roswell Park Comprehensive Cancer Center reports new data on the promise of combining standard treatment for breast cancer with a particular form of cancer immunotherapy — dendritic-cell (DC) treatment vaccines. This study, published in the Journal for ImmunoTherapy of Cancer, is the first to demonstrate that in situ dendritic-cell vaccines can improve the effectiveness of radiation therapy for some aggressive and treatment-resistant forms of breast cancer.
“Although immunotherapy with primary conventional dendritic cells is a promising approach, obtaining a sufficient number of circulating conventional dendritic cells has proved difficult,” says Dr. Ito, who is Associate Professor of Surgical Oncology at Roswell Park. Use of induced pluripotent stem cells (iPSCs) has been proposed to overcome that limitation, but the feasibility of this approach had not previously been demonstrated.
To better understand the potential of this approach, Dr. Ito and colleagues conducted laboratory studies to assess the antitumor efficacy of intratumoral injection of iPSC-DCs, or dendritic cells derived from iPSCs, and radiotherapy in models of triple-negative breast cancer that have shown resistance to anti-PD-L1 checkpoint inhibition immunotherapy.
The team’s results show that intratumoral administration of iPSC-DCs significantly enhanced antitumor efficacy of local irradiation, which is commonly incorporated into treatment plans for patients with breast cancer.
The researchers demonstrate that radiation therapy increased the trafficking of intratumorally injected iPSC-DCs to the tumor-draining lymph nodes and augmented the activation of tumor-specific T cells. Their work shows that this multimodal intralesional therapy can control growth of distant tumors and render some breast cancers responsive to anti-PD-L1 therapy
“While our work to develop this strategy is at an early stage and will need to be studied further, we show that these two approaches, radiotherapy and intratumoral iPSC-DC administration, can work synergistically to control not only local tumor growth but also distant tumors. And we saw evidence of systemic tumor-specific immunological memory, suggesting a potential for long-term tumor control,” says Dr. Ito.
This study sheds light on the antitumor efficacy of in situ administration of iPSC-DCs when integrated with radiotherapy against poorly immunogenic tumors. These findings align with another study from Dr. Ito and his team, recently published in Nature Communications, tthat showed potent systemic antitumor immunity caused by combinational multimodal intralesional therapy.
“Currently, efficacy of immunotherapy against breast cancer is limited,” adds Dr. Ito. “Our hope is to improve clinical outcomes for patients with advanced unresectable and metastatic breast cancer.”
This work, “In situ delivery of iPSC-derived dendritic cells with local radiotherapy generates systemic antitumor immunity and potentiates PD-L1 blockade in preclinical poorly immunogenic tumor models,” was supported by several grants from the National Cancer Institute (project numbers P30CA016056, K08CA197966, and R50CA211108), as well as the Melanoma Research Alliance, Sarcoma Foundation of America and Uehara Memorial Foundation.