Researchers Find Sarcoma Tumor Immune Response With Combination Therapy
A team of 18 researchers at Moffitt Cancer Center in Tampa, Fla., have found that treating high-risk, soft tissue sarcoma patients with a combination of implanted dendritic cells (immune system cells) and fractionated external beam radiation (EBRT) provided more than 50 percent of their trial patients with tumor-specific immune responses lasting from 11 to 42 weeks.
Their study was published in a recent issue of the International Journal of Radiation Oncology * Biology * Physics (Vol. 82, No. 2), the journal of the American Society for Radiation Oncology (ASTRO).
“Sarcomas are relatively rare forms of cancer with about 10,000 new cases in the U.S. annually,” said study co-author Dmitry Gabrilovich, M.D., Ph.D., senior member of the Moffitt Department of Immunology.
The authors note that because 50 percent of patients with large, high-grade soft tissue sarcomas develop distant metastasis, new, effective treatments are needed.
“Unfortunately, conventional therapy for large, high-grade tumors is frequently systematically ineffective, making this a very deadly problem,” Gabrilovich said.
According to the researchers, administration of dendritic cells has been found to be a promising method for producing an immune response because dendritic cells process antigen material and present it to other immune cells. Dendritic cells act as immune system messengers.
Combination Therapy Drives Cancer Into Remission
Researchers have achieved an experimental breakthrough in the simultaneous use of two or more agents for treating cancer, known as combination therapy. If it is shown to be safe and effective in humans, the therapy outlined by the new study is a promising general strategy for treating many cancers that do not respond to current therapies.
A two-drug combination therapy, published in tomorrow’s issue of the journal Nature, led to the complete remission of a mouse model of B-cell lymphoma in all of the treated animals. In contrast, animals treated with either drug alone (rapamycin or doxorubicin) rarely experienced complete remission.
The study, led by Dr. Scott Lowe of Cold Spring Harbor Laboratory, establishes a new paradigm for overcoming chemotherapy resistance in many forms of cancer.
Rational Target Selection and an Off-the-Shelf Chemotherapeutic “One-Two Punch” for Lymphoma and Other Cancers
Pre-cancerous cells can be eliminated from the body by a natural self-destruct mechanism-normally active in many types of cells-called programmed cell death. Unfortunately, a hallmark of most cancers is a defect in programmed cell death that enables pre-cancerous cells to survive, proliferate out of control, and form a tumor.
Because most traditional chemotherapy agents act by triggering programmed cell death, such agents are frequently ineffective against tumors that lack a functional programmed cell death mechanism. Such tumors are said to be chemotherapy-resistant. The evasion of treatment-induced programmed cell death by chemotherapy-resistant tumors has been a major impediment to successful therapeutic outcomes for human cancer.>
“Many studies have shown that preoperative radiotherapy and surgery is effective in treating many soft tissue sarcomas with high-risk features,” said Gabrilovich. “We designed our study to investigate the effect of combining the administration of dendritic cells and EBRT for patients with soft tissue, high-risk sarcomas.”
The researchers hypothesized that if dendritic cell implants were combined with EBRT (the most common kind of radiotherapy treatment that not only can kill tumor cells but release tumor antigens) the combination therapy might be complimentary when the dendritic cells helped process tumor antigens released by the EBRT treatment.
“The combination treatment resulted in dramatic increases in immune T cells in the tumors,” explained Gabrilovich. “The presence of T cells in the tumors positively correlated with the development of tumor-specific immune responses.”
An important finding in this study was that no patient had significant tumor specific immune responses before the combined therapy. After the combination treatment, tumor specific responses were observed in 52.9 percent of trial patients.