HER2 Antigen–Specific T Cells May Treat Sarcoma
Written by Leiomyosarcoma Team on 27 Apr 2015
A study at the Baylor College of Medicine in Houston, Texas used T cells that express a HER2-specific chimeric antigen receptor (CAR), showing promising as a treatment for HER-2 positive sarcoma in a small phase I/II trial.
The study, led by Stephen Gottschalk, MD wrote, “Immunotherapy with antigen-specific T cells may benefit patients with sarcoma because immune-mediated killing does not rely on pathways used by conventional therapies to which such tumors are often resistant.” The use of adoptive transfer of T cells that have been genetically modified to express CARs has shown promise in certain malignancies.
Researchers analyzed 19 patients with HER2-positive tumors including: 16 osteosarcomas, 1 Ewing sarcoma, 1 primitive neuroectodermal tumor, and 1 desmoplastic small round-cell tumor. These patients received escalating doses of HER2-CAR T cells. The median age of the patients was 17 years at the time of the T cell infusion. All patients included had metastatic or refractory disease, and had experienced treatment failure with at least one chemotherapy regime; 11 of 19 had undergone radiation therapy.
The study concluded that HER2-CAR T cells could be found in vivo in 14 of 16 evaluable patients who received doses above level 3 (1 × 105/m2). This dropped immensely after 3 hours beyond the infusion time. However, a low-level T cell signal could still be detected 6 weeks after infusion in seven of nine evaluable patients who had received a dose greater than 1 × 106/m2. Evidence of the HER2-CAR T cells in some patients found at 3, 6, 9, 12, and 18 months following infusion, suggesting that even without evidence of T cell expansion, the cells apparently do persist long-term.
The outcome resulted in 4 of 17 evaluable patients had stable disease for 12 weeks to 14 months. The median survival rate of the study was 10.3 months. The researchers wrote, “Targeting HER2 with antigen-specific T cells is an attractive strategy to expand HER2-targeted immunotherapies to malignancies that are HER2 positive but are insensitive to HER2 antibodies because they are not HER2 gene amplified.” They concluded that this study shows a safe dose of HER2-CAR T cells can be established, and that the cells can traffic to tumor sites and persist at low levels. “These data will facilitate subsequent clinical trials to further augment the expansion, function, and persistence of HER2-directed T cells.”