Synthetic Genomics and Advaxis have developed a current good manufacturing practice (cGMP) synthetic biology suite to produce synthetic DNA constructs. The cGMP facility meets U.S. Food and Drug Administration (FDA) requirements to begin a Phase 1 clinical trial testing ADXS-NEO — a potential immunotherapy made by Advaxis to treat a variety of cancers, including cervical cancer.
ADXS-NEO activates immune system responses against the unique mutations in each patient’s tumor, says Advaxis. The therapy primarily identifies neoepitopes – proteins that arise from mutations on tumor cells — that are not present on healthy cells. Then, with exome sequencing is used to develop a map of a patient’s tumor mutations to select which neoepitopes are most likely to trigger an immune response targeted at the cancer.
At the core of the suite is BioXp 3200 System Early Access Program, which gives researchers priority access to a personal DNA work station that delivers high-quality synthetic DNA fragments. The BioXp instrument can simultaneously build 32 unique double-stranded DNA fragments, virtually hands-free.
“This cGMP suite marks the first application of Synthetic Genomics’ automated DNA synthesis directed to improve patient care, and is a significant step towards moving synthetic biology from the benchtop to the bedside,” Oliver Fetzer, CEO of San Diego-based Synthetic Genomics, said in a press release. “The BioXp System and this first-of-its-kind cGMP suite opens the door to precision medicine, particularly when paired with the innovative technology Advaxis has developed for directing immune response towards cancer specific epitopes.”
Under strict cGMP process regulations, Synthetic Genomics uses a technology that is able to quickly convert the genetic sequences of these tumor-specific epitopes into synthetic DNA to create plasmid DNA targeting an individual patient’s cancer. Advaxis then combines these plasmid DNA with its MINE platform, designed to activate a patient’s immune system to respond against unique mutations – or neoepitopes – present in each patient’s tumor.
Every tumor cell presents antigens on its surface, much like small tags, that allows the immune system to recognize it. The MINE platform can target and sequence the DNA of these epitopes and find specific mutations that allow for a personalized immune therapy tailored for each patient tumor.
“Synthetic Genomics pioneered a synthetic DNA manufacturing process which has dramatically reduced turnaround time, from several months to just a few weeks,” said Daniel O’Connor, president and CEO of Advaxis, which is based in Princeton, New Jersey. “This process makes tailored immunotherapy feasible for critically ill cancer patients who don’t have time to wait. We have been impressed by the preclinical proof of concept work completed with Synthetic Genomics, and look forward to moving ADXS-NEO into human clinical trials.”