New Delhi: When a skin cancer tumour is surgically removed, the procedure does not necessarily mark an end to the patient’s ordeal. The cancer can return, sometimes more aggressively, in the same spot, in nearby lymph nodes, or in distant organs like the lungs and liver.
Immunotherapy such as pembrolizumab, the standard treatment given after surgery, does not work in all cases as cancer cells can develop resistance to it over time.
Now, a study suggests that pairing immunotherapy with intismeran, a personalized vaccine from the patient’s removed tumour using messenger RNA (mRNA) technology, could significantly reduce the risk of cancer recurrence.
Unlike the mRNA vaccines developed for COVID-19, which are designed to prevent infection before a person encounters a virus, Intismeran is a personalised cancer vaccine created after a patient’s tumour has been surgically removed.
The results of the phase 2b ‘KEYNOTE-942’ trial were presented at the 2026 annual meeting of the American Society of Clinical Oncology in Chicago and simultaneously published in the Journal of Clinical Oncology, on 1 June.
“Our study offers strong evidence to melanoma patients that Intismeran vaccine therapy, when used in combination with immunotherapy, can demonstrably reduce their risk of having their cancer return and improve clinical outcomes,” said Janice Mehnert, senior investigator of the study and professor at NYU Grossman School of Medicine.
“Our findings also serve as encouragement to cancer researchers globally that mRNA vaccines like intismeran could work well in combination with immunotherapy for other cancers whose high rates of mutations have proven difficult to target,” she added.
Melanoma originates in melanocytes, the cells that produce the pigment giving skin its colour. It is the most aggressive form of skin cancer because of its ability to spread rapidly to other organs.
In the US, an estimated 1,12,000 new cases are expected in 2026. It is comparatively less prevalent in India, occurring at roughly one-third to one-fourth the rate seen in the West.
This, according to Dr Chinlal Panihar, a consultant medical oncologist at New Delhi’s Kailash Hospital, is primarily due to differences in skin pigmentation. Higher melanin levels in darker skin offer greater natural protection against ultraviolet radiation, the main environmental trigger for melanoma.
Trial findings
The trial enrolled 157 patients across Australia and the US between 2019 and 2021. All had undergone surgery for advanced skin cancer that had spread to lymph nodes or beyond. Of these, 107 received intismeran plus pembrolizumab and 50 received pembrolizumab alone.
After more than five years of follow-up, 68.8 percent of patients on the combination therapy remained cancer-free, while 49.1 percent in the pembrolizumab-alone group had no signs of cancer. The combination also reduced the risk of the cancer spreading to distant organs by 59 percent.
“At four years, 72 percent of the patients were recurrence-free when both vaccination and immunotherapy were used, compared to 49 percent with immunotherapy alone. That is a difference of around 22 to 23 percent,” said Dr Gundavda.
“And if we look at distant metastasis-free survival at four years, it is 83 percent with the combination versus 65 percent with immunotherapy. So, there is a benefit of around 20 percent. The vaccine is definitely effective.”
Overall survival, the duration from diagnosis until death from any cause, was 92.2 percent for the combination group against 71.3 percent for those who received only immunotherapy. Seven patients died in each group during follow-up, mostly from cancer.
The science involved
Developed by American pharmaceutical major Moderna, intismeran is not a preventive vaccine like those meant for Covid.
“The COVID-19 vaccine was prophylactic, meaning the vaccination was given before the disease occurred. But here, intismeran is prepared from a patient who has already developed cancer and whose tumour has been completely removed. This is a recurrence-preventing vaccine,” explained Dr Panihar.
Once a tumour is surgically removed, scientists analyse a sample to identify unique markers—neoantigens—found only in cancer cells of an individual. Using this information, they create a personalised mRNA vaccine tailored for that patient.
The vaccine trains the immune system to recognise these cancer-specific markers and activate T cells, which can then find and destroy any remaining cancer cells.
This personalized vaccine is injected into muscle, in addition to pembrolizumab that is given intravenously. The two treatments work together to strengthen the body’s immune response against cancer, said Dr Manit Gundavda, Consultant, Orthopaedic Oncology (Bone and Soft Tissue Tumours) at Mumbai’s Kokilaben Dhirubhai Ambani Hospital.
“There is a synergistic action between the immunotherapy and the vaccine. The vaccine stimulates a T-cell response, further boosting immunity, while immunotherapy enhances the immune system’s ability to recognise and attack cancer cells,” he said.
T cells are a type of white blood cell that help the immune system by identifying and destroying infected, abnormal, or cancerous cells.
Dr Gundavda noted that the vaccine-immunotherapy combination is currently intended for patients with stage III or stage IV melanoma whose cancer had spread to the lymph nodes or other organs but has since been surgically removed. “These patients have no detectable cancer after surgery, and the treatment is given to reduce the risk of its return.”
In patients with early-stage melanoma, surgery is usually sufficient, and there is currently no established role for either immunotherapy or the personalised vaccine.
How vaccine works
Pembrolizumab works by blocking PD-1 (Programmed Cell Death 1), a protein found on the surface of T cells. PD-1 is often exploited by cancer cells as an “off switch” to hide from the immune system.
By blocking this pathway, pembrolizumab helps T cells recognise and attack cancer cells again.
However, melanoma is known for developing resistance to immunotherapy through immune evasion, wherein cancer cells find new ways to escape detection.
This is where intismeran adds a second layer of protection. Dr Gundavda explained that created using neoantigens—the abnormal, mutated proteins unique to a patient’s tumour—intismeran trains the immune system to recognise dozens of specific targets on cancer cells.
“In vaccination, we are inserting particular new antigens, around 30 to 40, and against those antigens, the immune system develops immunity. That is why the chances are lower for cancer cells to evade the immune response,” he explained.
In simple terms, pembrolizumab removes the brakes from the immune system, whereas intismeran gives it cancer-specific targets. Together, they make it more difficult for melanoma cells to escape immune attack.
Current evidence only shows the vaccine’s benefit when used alongside immunotherapy, Dr Gundavda cautioned.
As for whether the vaccine could eventually replace immunotherapy altogether, he said it was a question that cannot yet be answered, and for ethical reasons, should not be tested hastily.
“Right now, to answer that question would be like an ethical problem, because you would have to do a study where some patients only get the new vaccine without pembrolizumab, and that would mean that those patients are being denied standard of care,” he said. “Till this vaccine proves its efficacy, that it’s so good that it can be a replacement, it’s very early to answer that question.”
A larger phase 3 trial is already underway to validate these findings at scale. The vaccine is also being tested for its ability to prevent recurrence of lung cancer and other tumour types.
The findings will decide the possibility on whether this approach could eventually become a broader strategy against cancers that have so far been difficult to contain.
(Edited by Tony Rai)