DNA Vaccines 2014: A Spotlight on Intratumoral Immunotherapy

DNA Vaccines 2014: A Spotlight on Intratumoral Immunotherapy

31 July 2014,   By ,   0 Comments

Last week, sunny San Diego was the site of a big event (no, I don’t mean, Comic Con): the 2014 DNA Vaccine Conference hosted by the International Society of DNA Vaccines (ISDV). I thought I’d take the opportunity to describe some of the “best of conference, as seen through the completely biased eyes of OncoSec’s CMO and what it means for our mission of furthering intratumoral immunotherapy.

First of all, kudos to Inovio, who released positive phase 2 data on their DNA-based HPV vaccine in patients with cervical intraepithelial neoplasia 2/3 (CIN2/3) associated with HPV types 16 or 18. In this randomized, double-blind, placebo-controlled phase 2 study, histopathological regression of CIN2/3 to CIN1 or no disease was observed in 49.5% of treated patients compared to 30.6% of patients who received a placebo. This result was statistically significant (p<0.025) and indicated that the trial met its primary endpoint. Additionally, virological clearance of HPV 16 or 18 from the cervix was observed in 40.2% of treated patients compared to 14.3% of placebo recipients (p<0.025), meaning that the trial also met its secondary endpoint. We applaud their hard work and this good outcome for patients and we hope that this positive data will help validate electroporation as a clinically valuable drug delivery platform. I hope that studies such as these, ultimately, will help lend much-needed visibility to the entire field.

As Chairman’s Cup Sponsor for the event, OncoSec helped organize a session largely focused on intratumoral therapies, which included a number of very interesting talks.  Dr. Holbrook Kohrt and Dr. Ron Levy at Stanford have been two major proponents of intralesional therapy. Dr. Kohrt presented some compelling data, in both mouse models and lymphoma patients, demonstrating the ability of an intralesional TLR agonist (CpG) in driving systemic anti-tumor immune responses.

We were pleased to have Dr. Robert Andtbacka present an overview of key intralesional approaches that are currently in clinical trials, including data from the positive Phase 3 study of Tvec in melanoma, which he led. In this Phase 3 trial, Tvec achieved its primary endpoint of demonstrating a statistically significant increase in durable response rate (DRR) in patients with unresected stage 3b, 3c or 4 melanoma. Data showed that 16% of patients in the Tvec arm showed improvement compared to 2% in the control therapy arm. DRR was defined as the rate of complete or partial response lasting continuously for six or more months, as compared to the control arm. Tvec also appears to likely convey some benefit on overall survival.

Data showed a 4.4 month improvement in overall survival (HR=0.79; p=0.051), which came close to statistical significance in the overall patient population that included patients with and without visceral tumors. Andtbacka was hopeful that Tvec could become the first intralesional therapy to be approved in melanoma based on its ability to promote systemic anti-tumor responses! As you may be aware of, based on these data, Amgen and Merck have initiated a collaborative study investigating the combination of Amgen’s Tvec and Merck’s pembrolizumab.

DNA Vaccine Conference

“I believe these data, though preliminary, paint the picture that intratumoral electroporation of IL-12 is driving a conversion from a low to a high TIL phenotype” – Dr. Robert Pierce (Image by John Goode)

Both of these two talks paired very well with the presentation that I gave entitled “Intralesional DNA Immunotherapy: Converting Anti-PD-1 Non-Responders to Responders.” In this talk, I highlighted emerging data showing that – at least in melanoma – it is the high TIL/high PD-L1 patients, who represent the anti-PD-1 responder population and how the great unmet medical need now is figuring out how to convert low TIL into high TIL patients. In my opinion, we will need to reverse the immunosuppressive tumor microenvironment directly with local intralesional therapy, using potent pro-inflammatory molecules, like IL-12.  In support of this hypothesis, I showed some data from our patients treated with intratumoral electroporation of DNA-encoded IL-12 as well as some of our mouse model data. I believe these data, though preliminary, paint the picture that intratumoral electroporation of IL-12 is driving a conversion from a low to a high TIL phenotype and this supports our rationale for a combination approach with an anti-PD-1 (or, anti-PD-L1) mAb.

So as the sun set on the 2014 DNA Vaccine Conference and the scientists were shown the door by legions of costume-clad superheroes and such ilk, the sun was also rising on DNA vaccines and DNA-based intratumoral immunotherapy. I believe for a minute we all felt like superheroes…

“I Am ImmunoPulse!”

Main image by Miki Yoshihito


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