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Advaxis, City of Hope to Develop Listeria-Based Cancer Vaccine

Advaxis, a biotech firm developing cancer vaccines based on the Listeria monocytogenes bacterium, has inked a research collaboration with City of Hope to develop a new cancer vaccine targeting the p53 protein.
Although the collaboration at this point is “purely academic” as opposed to sponsored research, it could lead to the development of additional intellectual property in which both Advaxis and City of Hope would have a stake, according to an Advaxis official.
In addition, if the vaccine is efficacious in animal models, it would likely enter human clinical trials at City of Hope.
The collaboration is also the second major research partnership Advaxis has struck with an academic or research institution; the first is an ongoing research and licensing pipeline it has developed with the University of Pennsylvania.
John Rothman, vice president of clinical development for Advaxis, told BTW this week that the company hopes to forge additional similar partnerships with universities, research institutions, and hospitals in the coming months to broaden and further develop its vaccine technology platform.
“These are early days for us and early days for this work,” Rothman said. “We would very much like to collaborate. We are a very small biotech company. To the extent that we do have an interesting and effective way of delivering antigens, we are interested in partners, and finding people to work with.”
Advaxis’ Listeria-based vaccine technology uses modified Listeria monocytogenes to deliver a tumor-specific antigen fusion protein. It is based on research conducted by Yvonne Patterson, professor of microbiology at the University of Pennsylvania and chair of Advaxis’ scientific advisory board.
As such, as Advaxis progresses its HPV and p53 cancer vaccines to the clinic, it is obligated to pay UPenn undisclosed royalties and milestones “based upon the phase of development of clinical research … and the potential sales of agents, and then there are fees for every additional patent that is added to the portfolio,” Rothman said.
Advaxis’ current IP portfolio comprises some 60 patents, the bulk of which were developed at UPenn in the lab of Patterson or Fred Frankel, another microbiology professor at the school. Advaxis also has the right of first refusal for any related technologies developed by the UPenn scientists.
“Our relationship with Penn is pretty deep from our standpoint,” Rothman said. “I’ve given seminars and lectures there on several occasions. We have a very close relationship with Yvonne Patterson’s lab. We have a scheduled phone call with the lab once a week ... and we share information and review each other’s papers.”

“To the extent that we do have an interesting and effective way of delivering antigens, we are interested in partners, and finding people to work with.”

To a certain extent, he added, Advaxis has become a “placement office” for the lab in that most of the people working in Advaxis’ laboratories were previously post docs under Patterson. “There are not a lot of people that do this kind of work, so there are not a lot of people to draw from,” Rothman said.
Still, Advaxis is ready to branch out, and the City of Hope collaboration marks the beginning of that effort.
“We now have a postdoc that comes from another lab, and the company is beginning to grow a little bit,” Rothman said. “We are now beginning to develop technology in our own right and have filed patents in our own name, and we’re trying to develop this academic collaboration area.
“We believe that we have perhaps the best method of presenting antigens to the immune system as a delivery system, so we’re anxious to collaborate with other people,” he added. “We’re anxious to work with other people’s antigens, and make constructs for them in the hope that they’ll be more effective than the most common existing ways of presenting antigens to the immune system.”
‘Unusually Strong’
Advaxis’ construct has the ability to generate an “unusually strong” immune response to existing cancers and other diseases, according to Advaxis, and the company has had some success with another of its vaccines: Its lead Lm vaccine candidate, Lovaxin C, targets human papillomavirus-associated cervical or head and neck cancers. Advaxis recently completed a Phase I/II clinical trial for the vaccine, which demonstrated a high amount of efficacy in animal models and “some early efficacy in humans,” Advaxis said.
Under the City of Hope deal, Advaxis has created a new live Listeria-based vaccine, Adxs-LmddA159, which combines the strong immune activation of its Listeria technology platform with the antigen p53 tumor target to deliver the fusion protein LLO-p53 into the cells of the immune system for antigen presentation.
Joshua Ellenhorn, director of the department of general and oncologic surgery at City of Hope, will be the lead academic researcher on the project.
Advaxis’ Rothman said that Ellenhorn had been working with p53 for a number of years to try and exploit its involvement in a wide variety of cancers to develop vaccines. However, on its own, p53 is weakly immunogenic, Rothman said, and Ellenhorn was looking for another vector that was more immunogenic than some of the vectors he had worked with in the past.
“The director of our laboratories, Vafa Shahabi, was at a meeting where she ran into Dr. Ellenhorn … and the net result was that they decided a collaboration would make sense,” Rothman said. “They requested for us to create a p53 construct on a plasmid that Dr. Ellenhorn already had, and to give it to him to use and test within his model [animal] systems at City of Hope. We signed the appropriate material transfer and confidential disclosure agreements, made the construct for him, and he now has it.”
Rothman said that because p53 is so weakly immunogenic and difficult to make immunogenic — “many people have tried and many people have failed,” he said — that if Ellenhorn sees some initial efficacy in animal models with Advaxis’ construct, “then it would tell him that we have a very good way of doing things.”
Rothman also said that the collaboration is purely academic. Ellenhorn “gave us the plasmid, and we made the construct for him for nothing,” he said. Advaxis owns all of the IP for the technology at this point; however, if the project progresses, Ellenhorn’s lab and City of Hope could develop additional IP around the vaccine, for which the hospital and Ellenhorn would be compensated.
“It depends on where and how far it goes,” Rothman said. “It’s one thing to make a construct and put it into Dr. Ellenhorn’s hands, and clearly that’s our technology covered under the MTA. But going forward, if he does something in the clinic that makes sense, and tests patients in a way that make sense, I’m not sure what the IP would be.”
The ultimate goal of the partnership is to advance the vaccine to human clinical trials, which Rothman said would likely be conducted at City of Hope. “Dr. Ellenhorn is director of an oncology surgical unit at COH and he has access to patients, and if it works, he’d like to try it,” Rothman said.

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