A New Cancer Vaccine Draws Attention After Halting 23 Years of Breast Cancer

A new cancer vaccine in early human trials produced exciting results in a woman who had lived for 23 years with breast cancer and received 12 different treatments.

During the latest 6 months of follow-up, no signs of new or recurrent cancer were found. Scans also showed regression of a bulky distant left adrenal gland metastasis (cancer spread), as well as disease at other sites.

A Patient Who Had Battled Breast Cancer for 23 Years

Stephanie Gangi said she had been “emotionally and physically exhausted” before joining the new cancer vaccine study. Her longstanding diagnosis of hormone receptor-positive breast cancer and more than ten different treatments had not brought her to complete burnout. Instead, whenever a treatment failed, she could say “there was a next step to try, which was wonderful, and I had to keep going” .

“But I must admit that I am 66 and was tired of having cancer treatment for more than 20 years.”

Gangi, an essayist and fiction writer, said she was “cautiously optimistic” about the cancer vaccine, but “the main idea was that I wanted to avoid chemotherapy” .

“I wasn’t really signing up for spectacular results; I was signing up for something that could keep chemotherapy away. The biggest impact for me so far is that, for the first time in more than a decade, I am not taking any medication. That is really wonderful… and it means there are no side effects.”

Gangi’s vaccine treatment ended in July 2022. More than 3 months had passed since then, and she could hardly believe that her cancer was still regressing without medication. “I had breast cancer for a long time. You can’t just snap your fingers and be well.”

“Cancer is sneaky and malicious. It also knows how to evade every kind of treatment. But I am still happy and hopeful, and of course my family is very excited.”

Gangi was among a few participants in the phase 1/2 clinical trial at Mount Sinai School of Medicine in New York and was classified as having a “partial response” to the vaccine. One other patient had a partial response, and one had a complete response. However, 6 patients had progressive cancer and 1 had stable disease. The interim analysis of 10 patients yielded a 30% response rate. The results were presented at the Society for Immunotherapy of Cancer’s 37th annual meeting.

A Combination Cancer Vaccine

The vaccine being tested combines low-dose localized radiotherapy, dendritic cell stimulation through intratumoral Flt3L, the intravenously administered immune stimulant poly-ICLC and the PD-1 inhibitor pembrolizumab . This makes the approach a combination immunotherapy.

Lead author Dr. Thomas Marron, a hematology and medical oncology specialist, said that rather than making a vaccine in a laboratory and administering it, “we are actually formulating it inside the body.” “What people do not realize is that bulky tumor sites contain a lot of dead tumor because they grow so quickly and haphazardly. This means that the immune system can be enhanced to recognize the dead tumor and clear away dead material already there. We hope the immune system will kill not only the tumor injected but also tumors elsewhere in the body. Essentially, you are using the body’s own immune system and its on-off switches to vaccinate the patient against cancer.”

Another Patient With a Complete Response to the Vaccine

William Morrison, who had a complete response to the vaccine in the trial, had non-Hodgkin lymphoma. Diagnosed in 2017, he enrolled at that time in a phase 1 trial of an earlier version of this new vaccine treatment regimen. Speaking about that trial, Morrison said, “They basically did not get the results they hoped for, and I still had lymphoma.” In 2018, Morrison’s follicular lymphoma transformed into aggressive diffuse large B-cell lymphoma, and he received 6 cycles of chemotherapy. He entered remission, and his lymphoma cleared.

Morrison described what happened next: “But remission lasted perhaps a little over a year. The cancer returned, and at that point I had the opportunity to join the Mount Sinai trial. By the end of treatment, everything was clear. I went for a PET scan every 6 months, and I had another scan last week. Everything was fine… I was quite excited. I was very lucky. This last treatment really worked wonders. When they gave me the good news the other day, I felt a huge weight lift from my shoulders.”

Morrison also said he had no serious side effects during vaccine treatment. “Apart from a few minor things, I tolerated it quite well.” Gangi, by contrast, said she experienced “intense” flu-like symptoms that began within the first few days after treatment and lasted several more days.

The Response Rate Needs Improvement

Dr. Marron said that 30% of patients responded in the current trial, which was “wonderful, but we want it to be 100%” .

“We are now using this in the laboratory as an opportunity to examine what was special about the three responders and what was absent in the other seven. We already have some preliminary data that we are analyzing.”

“We see a much stronger response to Ft3L in the responding patients… This may suggest that we need a better Ft3L, or that we could consider other ways to manipulate this vaccine. Most patients referred to me have exhausted their treatment options… which generally means they have received many different kinds of chemotherapy. Gangi, for example, had already been through 12 different chemotherapy regimens.”

“Chemotherapy suppresses the immune system, but that is not all: the other treatments intended to reduce nausea and allergic reactions to anticancer treatment also have an effect. When I see patients, their immune systems are often not functioning optimally. Another way we might hope to see better responses is therefore to move this vaccine earlier in the treatment paradigm and give it as a first or second treatment.”

Coauthor Joshua Brody, director of the Lymphoma Immunotherapy Program at Mount Sinai’s Tisch Cancer Institute, said incorporating the vaccine into earlier lines of cancer treatment could be straightforward. “Both immunotherapy and radiation therapy are standard treatments, and the key is to bring together multiple components that do not have cumulative/additive side effects .”

“Combining two chemotherapies can cause more side effects than the sum of their separate effects, because they share some side effects. What is great here is that this therapy is quite safe. In theory, once we have a little more proof of principle, incorporating it into earlier treatment lines should be fairly straightforward.”

Dr. Ann W. Silk of Harvard Medical School and Dana-Farber Cancer Institute in Boston commented on the study: “The results are particularly impressive because we know that anti-PD-1 (pembrolizumab immunotherapy) plus radiation therapy does not work in hormone receptor-positive breast cancer or lymphoma. One advantage of this vaccine is that it is not restricted to a particular number of antigens and does not depend on an algorithm. I would very much like to see more data in patients with hormone receptor-positive metastatic breast cancer. I would use this approach after resistance to hormonal therapies develops but before chemotherapy. The safety profile looks quite good, and I expect it would result in much better quality of life than chemotherapy.”

Details of the Trial and Its Results

Mount Sinai researchers previously developed PGV-001, a promising personalized genomic cancer vaccine, in a phase 1 study involving 13 patients with solid (organ-based) tumors or multiple myeloma who had a high risk of recurrence after surgery or autologous stem cell transplantation.

They then worked to develop the concept further by turning a tumor into its own vaccine, combining Ft3L, low-dose radiation and poly-ICLC to trigger antitumor responses in indolent non-Hodgkin lymphoma, which generally responds poorly to checkpoint blockade. A subsequent phase 1 trial showed that the approach was feasible, but preclinical modeling suggested that adding PD-1 blockade could improve cure rates. The researchers therefore conducted the current trial in 10 patients with indolent lymphoma, metastatic breast cancer or head and neck squamous cell carcinoma.

Patients received localized radiation on days 1 and 2, and Ft3L into the same tumor on day 9, followed by 8 intravenous poly-ICLC injections over 6 weeks. On day 23, the first of 8 pembrolizumab doses was administered.

Dr. Marron described the trial as follows:

“Radiotherapy kills some tumor cells, increasing the amount of dead tissue for the immune system to work on. We are not trying to kill the whole tumor with radiation… It simply starts the process of releasing substances from that dead tumor tissue that can stimulate the immune system.”

“Ft3L is a human growth factor that stimulates dendritic cells, which I always call the immune system’s professors because they tell the body what is good and what is bad. Poly-ICLC is essentially like a fake virus: it activates immune cells around the tumor that have taken up tumor antigen, teaching the immune system that something bad is present. Finally, pembrolizumab is there to take the foot off the immune system’s brake and let the wheels turn a little faster, although it does not work in all patients or all tumor types, including indolent lymphoma.”

The trial was planned in two stages. The first enrolled six patients to assess safety. Phase 2 followed Simon’s Two-Stage design, including seven patients with each tumor type, with 12 more to be added if a response was seen. The current interim analysis presented at the Society for Immunotherapy of Cancer meeting focused on the first 10 patients enrolled between April 2019 and July 2022 in the phase 2 portion: 6 with metastatic breast cancer, 3 with indolent lymphoma and 1 with head and neck cancer. All had completed their first disease response assessment.

All patients experienced treatment-related side effects, mainly low-grade injection-site reactions and flu-like symptoms associated with poly-ICLC injections. One patient experienced grade 3 pembrolizumab-related colitis (inflammation of the large bowel) following a poly-ICLC injection, and another had grade 3 fever that resolved on its own.

In conclusion, this therapeutic cancer vaccine approach is complex, promising and remarkable as an indication of how far cancer science has progressed. Scientists will continue refining the technique to improve its effectiveness and test it in more patients.