ZIOPHARM Oncology Inc. (NASDAQ:ZIOP), a biopharmaceutical company focused on the development and commercialization of new cancer immuno-therapies, today 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, and was highlighted in a press release today by AACR.
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 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.
“Translating the remarkable effects of adoptive CAR T-cells from liquid to solid tumors can be challenging, as many solid tumor targets are found on healthy cells, creating the opportunity for toxicity,” said Laurence Cooper, M.D., Ph.D., Chief Executive Officer of ZIOPHARM and an author of the publication. “By targeting the density of tumor antigens, we have demonstrated an approach for preferentially killing cancer cells over healthy cells. In this case, the weakness of the nimo-CAR affinity is its apparent strength.”
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. (Original Source)
Shares of Ziopharm Oncology closed yesterday at $8.71. ZIOP has a 1-year high of $14.40 and a 1-year low of $2.31. The stock’s 50-day moving average is $11.27 and its 200-day moving average is $11.00.
On the ratings front, Ziopharm Oncology has been the subject of a number of recent research reports. In a report issued on August 10, J.P. Morgan analyst Cory Kasimov reiterated a Hold rating on ZIOP. Separately, on June 22, BMO’s Jim Birchenough downgraded the stock to Hold and has a price target of $10.
According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Cory Kasimov and Jim Birchenough have a total average return of 1.2% and 34.9% respectively. Kasimov has a success rate of 43.1% and is ranked #1682 out of 3742 analysts, while Birchenough has a success rate of 62.1% and is ranked #11.
Overall, 2 research analysts have assigned a Hold rating and 2 research analysts have given a Buy rating to the stock. When considering if perhaps the stock is under or overvalued, the average price target is $14.50 which is 66.5% above where the stock closed yesterday.
ZIOPHARM Oncology Inc is a biopharmaceutical company. The Company is engaged in the acquiring, developing and commercializing portfolio of cancer therapies that can address unmet medical needs through synthetic biology.