Syndicate content

Archive - Apr 15, 2017

Th17 Cells Do Not Lose Anti-Tumor Potency When Expanded Outside Body: New Findings in Mouse Model Have Implications for Advancing Field of Cancer Immunotherapy

In the March 9, 2017 issue of JCI Insight, Medical University of South Carolina (MUSC) investigators report that long-term expansion protocols for adoptive cancer immunotherapy do not compromise Th17 cells' effectiveness against large tumors. This finding is important because rapid expansion protocols (REPs) that are used to produce sufficient CD8+ T cell numbers for adoptive cell therapy (ACT) degrade their effectiveness. These findings underscore that Th17 cell durability offers promise for next-generation ACT trials. ACT is highly effective at activating the body's immune defenses to fight cancer. This immunotherapy involves extracting, expanding, and enhancing the patient's own T cells before returning them to the patient where they can induce a durable anti-tumor response. In fact, among metastatic melanoma patients treated with ACT, approximately 54 percent achieve an objective response and 24 percent achieve complete remission. However, infusion of large numbers of T cells is required to produce successful anti-tumor responses. Rapid expansion protocols meet this need, but take up to three months before enough tumor-reactive T cells are available to effectively treat cancer patients. In addition, the CD8+ T cells commonly used in clinical trials quickly lose potency when they are extensively expanded outside the body. The open-access JCI Insight article is titled β€œTh17 Cells Are Refractory to Senescence and Retain Robust Antitumor Activity After Long-Term Ex Vivo Expansion.” Preclinical studies by an MUSC research team led by Chrystal Paulos, Ph.D., Associate Professor of Microbiology and Immunology and Endowed Peng Chair of Dermatology and including Medical Scientist Training Program (MSTP) student Jacob Bowers, demonstrate for the first time that one T cell subset, Th17 cells, is resistant to expansion-induced degradation.

Immunotherapy for Glioblastoma Well Tolerated; Survival Gains Observed in Small Phase One Trial at Duke; Results Support Further Study in Larger Trials

A phase one study of 11 patients with glioblastoma who received injections of an investigational vaccine therapy and an approved chemotherapy showed the combination to be well tolerated, while also resulting in unexpectedly significant survival increases, researchers at the Duke Cancer Institute report. Patients treated with the study drug (dose-intensified temozolomide and vaccines) were continuously monitored for toxicity and adverse events. Study patients experienced known side effects with temozolomide, including nausea, lymphopenia, thrombocytopenia, and fatigue. There were no treatment-limiting adverse events and no adverse events related to the cellular portion of the vaccine. One patient developed a grade 3 vaccine-related allergic reaction to the GM-CSF component of the vaccine. The patient was able to continue vaccinations in which the GM-CSF was removed and had no subsequent adverse events. Although the trial was small and not designed to evaluate efficacy, 4 of the 11 study patients survived for more than five years following treatment with a combination of vaccine and the drug temozolomide, a first-line chemotherapy drug for glioblastoma. That outcome is uncommon for glioblastoma, a lethal brain cancer that has a median survival of nearly 15 months when treated with the current standard of care. "This is a small study, but it's one in a sequence of clinical trials we have conducted to explore the use of an immunotherapy that specifically targets a protein on glioblastoma tumors," said Duke's Kristen Batich (photo), M.D., Ph.D., lead author of a study published online on April 14, 2017 in the Clinical Cancer Research.