The History and Future of Cancer Vaccines at MSK

Remarkably, the idea that a patient’s own immune system could fight cancer is more than a century old.

The first notion of a cancer vaccine came back in 1893. Memorial Sloan Kettering Cancer Center (MSK) bone surgeon and cancer researcher William Coley, MD, noticed that patients with bacterial infections sometimes saw their tumors shrink, which hinted that the body’s own immune system could be a weapon against cancer. More than 130 years later, researchers at MSK have continued to build upon Dr. Coley’s early ideas, breaking new ground and driving the field now known as “immunotherapy” forward.

Today, one specific type of immunotherapy — therapeutic cancer vaccines — has taken center stage. Unlike traditional vaccines, which prevent disease, a cancer vaccine would actually treat the disease. The concept is audacious. It is challenging. And it is also achievable, thanks to new technology and more support for researchers in the lab and the clinic.

How COVID mRNA Vaccines Helped Boost Cancer Vaccine Research

David Scheinberg, MD, PhD, has been soldiering in the field for more than 20 years as a leader of immunotherapy drug development at MSK.

“For a long time, cancer vaccines didn’t show much promise, and people were skeptical,” he says. “But the success of the COVID vaccine generated a lot of enthusiasm and has renewed interest in cancer vaccines — and that is great news for everyone working in this field.”

The COVID vaccine demonstrated that it’s possible to use mRNA technology to train the immune system to ward off virus invaders, known as pathogens. It’s a preventive vaccine.

A cancer vaccine also engages the immune system, but in a slightly different way. It’s a therapeutic vaccine, which works by exposing the immune system to the specific proteins produced by a patient’s tumor, called antigens. Once the immune system sees those rogue proteins, it will attack them and keep the cancer at bay.

The Challenges and Benefits of a Therapeutic Cancer Vaccine

Developing therapeutic cancer vaccines is a major challenge because cancer cells are the enemy within. A person’s own cells are turning against them and growing out of control. Therefore, cancer vaccines must teach the immune system how cancer cells differ from the rest of the body.

If that goal can be achieved, Dr. Scheinberg says that therapeutic cancer vaccines offer important advantages over other cancer treatments:

• They can be given over a brief period and then are not needed again, as the immune system learns to fight on its own.
• Side effects are lower compared with more toxic treatments such as chemotherapy or radiation therapy.

In the past, Dr. Scheinberg explains, several challenges prevented cancer vaccines from meeting their full potential:

• They were too narrowly focused, targeting just one antigen. “Tumors have different antigens from cell to cell,” he says. “Some tumor cells are attacked, but others survive and grow.”
• They were given to patients with too much cancer in the body; they didn’t have enough power to conquer tumors, which can suppress immune attacks by masking their own antigens. Cancer cells can also send out signals to immune cells to reduce their efficiency.

The Potential of Cancer Vaccine To Prevent Cancer Recurrence

“Therapeutic cancer vaccines usually cannot wipe out an existing tumor or make bulky amounts of cancer go away,” Dr. Scheinberg says. “They work much better to prevent cancer from coming back after the tumor has been removed by a surgeon or put into remission by chemotherapy or radiation.”

He points to the phenomenal success of the HPV vaccine in preventing the HPV virus from infecting cells and causing them to develop into cervical cancer.

“We know vaccines can stop cancer from forming — the same principle holds when the cancer is largely gone,” Dr. Scheinberg says. “When people say cancer vaccines just will not work, they are wrong. They do work — if they are specific, potent, attack multiple antigens, and are given when there is not much cancer in the body.”

That’s now possible, thanks to new technology.

“The science has evolved, and the clinical applications have evolved, which are contributing to the new optimism,” says Dr. Scheinberg.

The momentum for cancer vaccines picked up speed in 2024 with a generous gift supporting The Olayan Center for Cancer Vaccines (OCCV) at MSK, now a critical part of MSK’s broader efforts to develop immunotherapies. It will expedite development of vaccines that target a wide range of cancers.

“This center is a unique, visionary initiative that will enable our researchers and clinicians to develop breakthroughs for people with cancer,” says MSK surgeon-scientist Vinod P. Balachandran, MD, Director of the OCCV.

Personalized mRNA Cancer Vaccines for Pancreatic Cancer

Dr. Balachandran has played a key role in the development and testing of one of the most exciting examples of this type of therapy: a vaccine for treating pancreatic cancer based on mRNA. It is personalized for every patient, based on their tumor’s particular antigens.

Dr. Balachandran led a phase 1 clinical trial showing that the mRNA-based vaccine, given after surgery to remove pancreatic tumors, stimulated the production of immune cells that recognized the antigens in the pancreatic tumors.

The investigational vaccine, called autogene cevumeran, was developed through a collaboration between BioNTech and Genentech. In November 2024, updated results from the phase 1 trial showed that the immune cells targeting the tumor antigens had persisted for more than three years. There is an ongoing phase 2 study to determine whether that means the vaccinated patients live longer.

None of this research would be possible without the ability to track these activated T cells with the help of computational biologist Benjamin Greenbaum, PhD, Co-Director, Neoantigen Discovery, OCCV. “The way that computational biologists and physician-scientists collaborate is especially strong at MSK,” Dr. Greenbaum says. “I don’t think this research confirming the vaccine’s effects on the immune cells would happen at other places.”

How MSK Is Developing Off-the-Shelf Cancer Vaccines To Make Treatment More Accessible

Personalized vaccines are one vaccine strategy – MSK researchers are also working to develop off-the-shelf vaccines, which target features present in many patients’ tumors. 

One key to off-the-shelf cancer vaccines: finding and targeting an antigen that is present in most cancer cells but not normal cells.

Acute Myeloid Leukemia

Again, MSK researchers are leading the way. Dr. Scheinberg has developed a vaccine targeting an antigen called WT1, found in the cancer cells of more than 95% of people with acute myeloid leukemia (AML), ovarian cancer, and mesothelioma. It is a complex “peptide” vaccine that triggers a targeted immune response by using synthetic peptides, which are strings of amino acids — the building blocks of proteins.

This WT1 peptide vaccine is now being tested in an international phase 3 clinical trial for AML, sponsored by Sellas Life Sciences Group Inc. Dr. Scheinberg is a Director of Sellas. “These off-the-shelf vaccines in development could potentially be available to patients — they can be mass-produced and sit in a vial in a refrigerator, ready to be used,” Dr. Scheinberg says. “This could make them possibly more accessible and more affordable, which can be critical in helping the most patients.”

Peptide-Based Vaccine for Pancreatic and Colorectal Cancer

Another off-the-shelf, peptide-based vaccine is being tested for pancreatic and colorectal cancer in a clinical trial co-led by medical oncologist and pancreatic cancer specialist Eileen O’Reilly, MD. The phase 1 trial involved patients whose cancer had mutations in a gene called KRAS and were at high risk of the cancer returning after surgery. The results demonstrated this vaccine is safe and appears to stimulate the patient’s immune system to create cancer-fighting cells.

“These findings show we have more than one way to activate immune cells to target pancreatic cancer,” Dr. O’Reilly says.

Scientists are also excited about the possibility of using cancer vaccines to boost the effectiveness of other therapies. The pace of progress since Dr. Coley’s discovery more than a century ago has accelerated dramatically in the past few years. Once believed unattainable, cancer vaccines are now full of possibility.

“We have made tremendous leaps over the last two decades understanding how the immune system recognizes and kills tumors,” Dr. Scheinberg says. “These insights are what will help make cancer vaccines — and other immune-based treatments — a reality for more patients.”

Pancreatic Cancer Vaccine Gives Patient Extra Years  

One of Dr. Balachandran’s patients in the phase 1 study, Barbara Brigham, is still doing well four years after being diagnosed with pancreatic cancer, beating the odds for this particularly deadly cancer. After surgery to remove her tumor, she received an immunotherapy drug and then two doses of the mRNA vaccine based on the molecular structure of her tumor, followed by chemotherapy.

“I’m so glad I decided to participate in this trial,” she says. “I feel good and have been working part time at the library, playing mahjong with my friends, and spending more time with my grandchildren — enjoying things that at one point I never thought I’d have.”