Date: 2015-09-01
Type of information: Publication of results in a medical journal
phase: preclinical
Announcement: publication of results in Cancer Research
Company: Ziopharm Oncology (USA - MA)
Product: cetux-CAR T cells, nimo-CAR T cells
Action
mechanism: immunotherapy product/cell therapy/gene therapy.
Disease:
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On September 1, 2015, Ziopharm Oncology, a biopharmaceutical company focused on the development and commercialization of new cancer immuno-therapies, announced the publication of a preclinical study in Cancer Research, a journal of the American Association for Cancer Research, demonstrating the preferential targeting of solid tumor cells over healthy cells using engineered chimeric antigen receptor (CAR) T cells. The article, titled "Tuning sensitivity of CAR to EGFR density limits recognition of normal tissue while maintaining potent anti-tumor activity," is available online first at cancerres.aacrjournals.org. Abnormally-expressed antigens on tumors, such as epidermal growth factor receptor (EGFR) on aggressive brain tumors such as glioblastoma, can be overexpressed relative to lower, basal levels on normal tissues. Taking advantage of this observation, researchers at The University of Texas MD Anderson Cancer Center tuned the binding affinity of CARs to activate T cells based on the density of EGFR expression. The approach was based on the clinical toxicity exhibited by the EGFR-specific antibodies cetuximab and nimotuzumab, which recognize overlapping epitopes and exhibit different kinetics of binding to EGFR. The lower affinity of nimotuzumab has been credited with absence of adverse events relative to cetuximab. Researchers engineered high-affinity cetux-CAR T cells and low-affinity nimo-CAR T cells, which were tested in vitro on cancer cells with high levels of EGFR, and normal cells with low levels of EGFR. It was found that, while the cetux-CAR T cells killed both cancer and normal cells, the nimo-CAR T cells were selectively activated only in response to cancer cells. The researchers then tested the CAR T cells in mice bearing human brain cancer cells expressing high levels of EGFR and found that both cetux- and nimo-CAR T cells were equally effective in inhibiting tumor growth. However, the cetux-CAR T cells caused significant toxicity to the mice, leading to death in some, whereas the infused nimo-CAR T cells were safe. The researchers further tested the new CAR T cells in mice bearing cells that had low levels of EGFR (to mimic normal human cells), and found that unlike cetux-CAR T cells, the nimo-CAR T cells did not impact the growth of these cells. The researchers then tested the two populations of genetically modified T cells in mice bearing human brain cancer cells expressing high levels of EGFR and found that both cetux- and nimo-CAR T cells were equally effective in inhibiting tumor growth. However, the cetux-CAR T cells caused significant toxicity to the mice, leading to death in some, whereas the infused nimo-CAR T cells were found to be safe. The researchers further tested both CAR T cells in mice bearing cells that had low levels of EGFR (to mimic normal human cells), and found that unlike cetux-CAR T cells, the nimo-CAR T cells did not impact the growth of these cells. Ziopharm is developing various immuno-oncology programs, including CAR-T, TCR and natural killer (NK) adoptive cell based therapies, in collaboration with the MD Anderson Cancer Center and its partner Intrexon Corporation.
