Applied DNA Sciences Inc. (NASDAQ: APDN), a leader in large-scale PCR-based DNA manufacturing, announced today that LineaRx, Inc. (“LineaRx”), its majority-owned subsidiary focused on next-generation biotherapeutics, and its collaborators Takis/Evvivax have completed pre-clinical animal studies of two vaccine candidates produced with linear DNA. Tests of both vaccines in mouse models demonstrated their ability to eliminate tumors in vivo, and to potentially prevent initial occurrence.

Evvivax S.R.L. designed a synthetic gene sequence to produce immunity in companion animals, directed against the protein telomerase (TERT), which is overexpressed in 85% of all mammalian cancers, whereas Takis S.R.L. designed a neoantigen-based cancer vaccine (TK), as a proof-of-concept of personalized immunology. For the studies, the TERT and TK based vaccines were produced in linear DNA form by LineaRx. Here is a summary of the recently completed studies performed in vivo:

• Previous results from Phase 1 of the collaboration’s Joint Development Agreement (JDA) confirmed immunogenicity in mice that were vaccinated with linear DNA against the human protein telomerase. The results reported herein are from the Phase 2 of the JDA using mice implanted with murine colon cancer.
• In the prophylactic use of the telomerase vaccine, wherein vaccination is done before addition of tumor cell lines to the mice, transplanted tumors were cleared within 10 days.
• In the therapeutic application using either TERT or TK linear DNA vaccine application, cancer cells were introduced and allowed to grow before administration of the vaccine. The successful reduction of total tumor mass was accomplished in conjunction with antibodies that targeted PD-1 and CTLA4. These antibodies, known as Checkpoint Inhibitors, are commonly used in oncology strategies that rely upon immunotherapy. In this setting the tumor cells were reduced significantly within 30 days.
• The strategy of the Takis TK neoantigen vaccine uses unique multiple-target antigenic epitopes that have been identified from the tumor of a human patient. The linear DNA can utilize the genes for several of the most effective universal antigens such as TERT, or neoantigens that are more personalized to the patient.

“We know that immune system has a key role in fighting cancer,” said Dr. Luigi Aurisicchio, CEO of Takis/Evvivax. “Thanks to a deep knowledge of cancer immunobiology and cutting-edge vaccination technologies we have now the tools to provide new therapies to our pet friends and human patients.”

“Our unique triumvirate of JDA partners is compelling, in that clinical data accumulated from linear DNA vaccines for companion animals can be used to accelerate translation to human therapies by Evvivax and Takis,” said Dr. James Hayward, president and CEO of Applied DNA and LineaRx. “Cancer vaccines would extend the lives of many family pets, and the benefit we believe would rapidly enure to humans.”

Linear DNA vaccines are being spearheaded by LineaRx to drive more efficient production methods and what are believed to be safer therapies for patients. Current production standards for human DNA vaccines use the circular DNA of plasmids that are grown in bacteria. However, this raises concerns regarding the risk of integration of bacterial genes including the antibiotic-resistance genes into the human genome or transfer into commensal bacteria, that are a normal part of the human bacterial flora.

Dr Aurisicchio concluded, “The advantages of linear DNA should improve the safety and efficacy of all gene therapies, both in animals as well as humans.” The JDA partners expect to publish their results in the scientific literature soon and will initiate planned Phase 3 work in companion animals.