Delivery Matters: In Early Studies, DPX Technology Allows Vaccines to Persist When Cancer Pushes Back

Evidence-Based OncologyApril 2023
Volume 29
Issue 4
Pages: SP270

Based on promising results, the biotech IMV has moved into phase 2b trials with a cancer vaccine composed of survivin epitopes that uses the company’s proprietary delivery system to elicit persistent immune responses.

As cancer treatments have evolved, scientists have worked to improve 2 things: making the responses to therapy last longer, and limiting how much collateral damage the therapy does as it attacks the tumor. The arrival of immunotherapy has been monumental: across many types of cancers, response rates to immunotherapy are higher, deeper, and more durable than with chemotherapy.1 When responses occur, adverse events in immunotherapy are different but manageable, and quality of life is improved.

Still, not every patient benefits. Not everyone responds, and despite the advances of the last decade, some cancers have high rates of recurrence; ovarian cancer, for example, has a rate of 85%.2 For all the wonders of chimeric antigen receptor (CAR) T-cell therapy in diffuse large B-cell lymphoma (DLBCL), about 40% of patients relapse.3 Thus, the quest continues for treatments that last longer with fewer adverse events (AEs); in the United States, this may also allow the patient to keep a job that provides health coverage.

It's these highly refractory patients that the biotech IMV is enrolling in trials, so it can examine its novel delivery platform for immunotherapy, one designed to teach the body’s immune system—including the innate immune system—to deliver a sustained response against cancer. Based on promising results, including the SPiReL study in DLBCL,4-5 IMV has moved into phase 2b trials in both DLBCL and ovarian cancer with its lead therapeutic candidate, maveropepimut-S (MVP-S), which is a cancer vaccine composed of survivin epitopes that uses the company’s proprietary delivery system, called DPX.

The VITALIZE Phase 2b trial (NCT04920617) is a randomized, parallel group 2-stage study that will evaluate MVP-S with pembrolizumab (Keytruda) in patients who have received at least 2 lines of systemic therapy and are ineligible for or have failed autologous stem cell transplant (ASCT) or CAR T therapy. Positive preliminary data from VITALIZE were shared February 13, 2023, at the IO 360 meeting in New York, New York.6 Data shared showed:

  • among the 8 patients with an ECOG score of 0-1 enrolled, 6 were evaluable for efficacy; 3 had confirmed complete responses, 1 patient was assessed with stable disease; 2 were assessed with progressive disease; and
  • 2 patients with ECOG scores of 2 or greater failed to stay on the study through first scan, and could not be evaluated.

A phase 2b, single-arm study called AVALON (NCT05243524) involves MVP-S with intermittent low-dose cyclophosphamide in patients with platinum-resistant ovarian cancer.7 The MVP-S agent with pembrolizumab combination is also being studied in bladder cancer.8

Vaccines That Persist in Fighting Cancer



In an interview with Evidence-Based Oncology,™ (EBO) prior to the IO 360 presentation, Jeremy Graff, PhD, explained the science behind the DPX platform. Most people are familiar with prophylactic vaccines—such as those that prevent polio, measles, or COVID-19—which he said are used “to prevent a disease from taking root.” Therapeutic vaccines, Graff said, must accomplish a different task. Not only must they create a response that works immediately against the disease, but they must also generate a response that is persistent, meaning it keeps working against the disease despite the microenvironment that the cancer or chronic illness has setup to insulate against an attack.

With a prophylactic vaccine, “When we educate our response to poliovirus, there's nothing that pushes back against that response,” Graff explained. By contrast, “when we educate a response to a cancer protein, the cancer itself is pushing back against that response all the time.”

Cancer vaccines have failed in the past, he said, because they have not generated this persistent response. Prior efforts have tried to deploy a prophylactic strategy, with the hope that would become therapeutically useful. Instead, Graff said, the immune response is temporarily ignited but ultimately shuts down, “in many cases by the cancer itself.”

DPX takes an entirely different approach by packaging its vaccine, or other cancer-fighting cargo, in a way that ignites the innate immune system, so that it “digests” the key antigens “that we want the immune system to pay attention to,” he said. Instead of flooding the patient with poorly targeted chemotherapy or more precise immunotherapy, Graff explained, the DPX platform works to hand deliver antigens with the right signals to the T cells and B cells of the adaptive immune system, so they are trained in waves to fight cancer.

Carrying the Cargo in Oil

“Our formulation is very different,” Graff said. “We resuspend our immune-educating cargo, whether they’re antigens in the form of proteins, or peptides, or RNAs, in an oil. And then we inject that oil-based solution into the subcutaneous space.”

The solution stays put until the antigen-presenting cells of the innate immune system arrive to carry the injection to the lymph nodes, where they can work against cancer. Prior systems just let vaccines “fall part” in tissue, Graff explained.

It takes time to carry the injection to the lymph nodes, and with the DPX system investigators allow 60 days for the vaccine to be carried through the immune system; then another injection starts the process again. EBO asked Graff: does each patient’s innate immune system deliver the vaccine on the body’s own timetable—creating, essentially, a new type of personalized medicine?

“You can kind of think of it that way,” Graff responded. When the antigen-presenting cells pick up on the vaccine, they do so along with whatever bacteria, fungi, or viruses an individual already brings to the system. Whatever the immune system looks like, the antigens still train the T and B cells.

Can the DPX technology, with its oil-based solution, work with other cancer-fighting agents besides what is currently under study? Graff says yes. “We think we can take all different types of cargo,” he said. The lead product is licensed from Merck KGaA (Germany); it had been tested with a standard emulsion, but no clinical benefit was seen. Used with DPX, Graff said, “We now see a much more robust immune response—it’s much more persistent. It leads to clinical benefit and has done so in multiple cancer types.”

Could this mean that molecules that showed promise in mouse models but didn’t pan out in early human trials could see new life with DPX technology?

“Absolutely,” Graff says enthusiastically. “We can package whole viruses, we can package large proteins, multiple proteins, antigens, RNAs—we can do all sorts of stuff with our formulation,” he said.

“We would say in a short way, delivery matters,” Graff said. “If you don't deliver antigens to the immune system correctly, you can't expect the immune system to react correctly.”

Will the Markets Respond?

Despite the previous findings and well-received preliminary VITALIZE data presented at IO 360, IMV finds itself in a quandary. In a March 16, 2023, conference call to discuss annual fiscal year-end financials, CEO Andrew Hall was at a loss to explain the recent sell-off of IMV shares. “That fact that we have seen the same number of complete responses in the first handful of patients as we had seen for the whole SPiReL trial, and those complete responses have been confirmed by at least 2 scans—one at 70 and one at 140 days—is, to say the least, encouraging,” he said during the call.9

The current financial landscape for small biotechs is challenging, Hall said. “It's for this reason, we've engaged our long-time partner, Stonegate, to help us explore strategic options in this difficult market,” he said.

Hall also wanted investors to understand just who the patients are that IMV is reaching. “I want to highlight one of those complete responses in VITALIZE that was presented at the recent IO 360 meeting in New York. This patient is young man, 24 years old. His disease had progressed through standard rituximab-based therapy, then stem cell transplant, and, more recently, through CAR T therapy.”

“He was running out of options,” Hall continued. “He enrolled in the VITALIZE trial last fall. On his first scan 70 days later, his disease was gone. On his second scan, he is a complete confirmed responder. For the first time since diagnosis, this patient is back at the gym and doing things a 24-year-old should be doing.”

Graff explained why 2 patients could not stay on study. The trial criteria call for patients to have a life expectancy of at least 90 days; some patients simply are not making it through the screening phase.

In its March 16, 2023, statement, IMV said it will complete stage 1 enrollment in VITALIZE (30 patients) during the second quarter of 2023; it will complete stage 1 enrollment of AVALON in the third quarter of 2023 (approximately 40 patients), and will present preliminary phase 1 data involving MVP-S and the DPX platform in non-muscle invasive bladder cancer in third quarter of 2023.10


1. Zhang Y, Zhang Z. The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol Immunol. 2020;17(8):807-821. doi: 10.1038/s41423-020-0488-6

2. Blevins Primeau AS. Cancer recurrence statistics. Cancer Ther Adv. November 30, 2018. Accessed March 21, 2018.

3. Larson RC, Maus MV. Recent advances and discoveries in the mechanism and functions of CAR T cells. Nat Rev Cancer. 2021;21(3): 145–161. doi: 10.1038/s41568-020-00323-z

4. Berinstein NL, Bence-Buckler I, Forward NA, et al. Clinical effectiveness of combination immunotherapy DPX-Survivac, low dose cyclophosphamide, and pembrolizumab in recurrent/refractory DLBCL: the SPiReL study. Presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 4-8, 2020; virtual. Abstract 2114.

5. IMV’s survivin-targeted T cell therapy shows durable clinical benefits in phase 2 study in patients with hard-to-treat advanced recurrent ovarian cancer. News release. IMV Inc. December 3, 2020. Accessed March 21, 2023.

6. IMV Inc. presents positive initial results from the MVP-2 phase 2b VITALIZE trial. News release. IMV Inc. February 13, 2023. Accessed March 21, 2023.

7. IMV Inc. announces update and planned 2023 milestones to advance clinical development of its lead therapeutic, MVP-S. News release. January 8, 2023.

8. Our clinical pipeline. IMV Inc. Accessed March 21, 2023.

9. Fourth quarter and fiscal year 2022 results webcast. IMV Inc. website March 16, 2023. Accessed March 17, 2023.

10. IMV Inc. announces strategic update as well as fourth quarter and full year 2022 and financial and operational results. News release. IMV Inc. March 16, 2023. Accessed March 17, 2023.

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