Neoantigens Revive Vaccine Opportunities in Immuno-Oncology

Neoantigens are novel proteins that form on cancer cells following the development of mutations in the tumor-cell DNA. These proteins are new to the immune system and are not part of the collection of self-proteins to which immune cells are tolerant or non-responsive. Therefore, neoantigens have the ability to trigger an impressive and very specific immune response, which has piqued the interest of immunology experts and garnered much-deserved attention from scientists in recent years. Let’s take a closer look at the progress being made in the fight against cancer and the challenges these revolutionary therapies face.

Why Are Immunology Researchers Focused on Neoantigens

Neoantigens are specifically found in or on tumor cells and can be highly immunogenic. While traditional treatments for cancerous tumors such as chemotherapy, radiation therapy, and surgery are still widely used, researchers are making strides in neoantigen immunotherapies to combat malignant forms of cancer.

The key to using neoantigens as part of an immuno-oncology therapeutic strategy is that these proteins are only associated with diseased cells or tissue and are not expressed by healthy cells. This provides a highly specific therapeutic target that can be administered as a vaccine. Such a vaccine would actively stimulate a patient’s immune system to produce an anti-tumor response while resulting in minimal autoimmunity. Although the research and development of this technology are still in its infancy, the concept of a ‘cancer vaccine’ offers researchers a promising new direction in the fight against cancer.

Sharon Benzeno, Chief Business Development Officer at Adaptive Biotechnologies, weighs in, “Antigens are proteins or pieces of proteins that either already exist in our bodies, ‘self’ antigens, or ‘foreign’ antigens that come from outside the body, such as pathogens or viruses. In some cases, foreign antigens are created when normal proteins in healthy cells mutate and trigger cancer disease signals.”

In oncology, neoantigens are a distinctive feature of cancerous tumors that are not part of the normal repertoire of proteins in a patient’s body. A patient’s T cells have developed to recognize only “non-self” antigens. In healthy individuals, this prevents autoimmunity or a condition in which the body attacks its own cells. However, since the neoantigens were not part of this process, the patient’s immune system can recognize neoantigens in the same way they would recognize foreign antigens. Research has shown that introducing these novel neoantigen proteins in the form of a vaccine will promote the expansion of neoantigen-specific T cells which will then seek out tumor cells and kill them.

Chief Scientific Officer at Genocea Jessica Flechtner adds, “Neoantigens are unique because the mutations that occur in the DNA change the coding region of these proteins. Suddenly, parts of the tumor look foreign to your immune system; you are no longer trying to overcome the tolerance to ‘self’; you are encouraging the immune system to pay attention to the tumor like it was an invading pathogen.”

The Future of Cancer Vaccines

According to Flechtner, “So far we have just scratched the surface of what we can do to help them with neoantigen vaccinations. You can elicit immune responses in those patients to their own tumors. It is relatively safe, which is one of the problems with other treatment modalities in cancer, where they can cause a lot of toxicity to a patient that is already sick. It shows we are on the right track by trying to work towards neoantigen vaccinations.”

However, Flechtner admits that some of the data have been discouraging. “The clinical data has been ambiguous and somewhat hard to interpret. In some cases, it looks like the vaccine has a positive impact, but in other cases, you cannot tell whether it was the vaccine or perhaps a drug that it was co‑administered with. There is some way to go.”

In the last decade, there has been a shift away from a one-size-fits-all approach to healthcare in favor of personalized medicine. Broadly, a personalized treatment plan focuses on utilizing a patient’s unique genetic and/or biomarker information to make treatment decisions on their behalf. That’s another reason why immunologists have a vested interest in neoantigen vaccines. Each patient can express unique neoantigen components in their tumors. Neoantigen vaccines would therefore need to be tailored to treat a patient’s unique set of mutations to spare the healthy cells and target the cancer cells. This patient-centric approach improves the projected success of this type of therapeutic, however, the challenge presented is whether the group of neoantigens extracted to create the vaccine will generate an effective T cell or immunogenic response.

Sharon Benzeno wanted to point out that neoantigen-based vaccines can treat different cancer antigens at once rather than having to administer a toxic combination of traditional treatments that can be hard on the patient over the course of a treatment plan.

Challenges of Neoantigen Vaccines

From patients to physicians, the mere mention of a ‘cancer vaccine’ gets people excited. But this may be premature. While researchers admit that the possibilities are endless and some promising results with neoantigen vaccinations have been realized, there have been significant challenges as well. But in science, challenges are meant to be overcome.

Due to the overwhelming amount of neoantigens, which is currently estimated in the hundreds, researchers will need to decipher which neoantigens are the most effective by “including additional new classes of tumor-specific neoantigens,” to successfully design a neoantigen vaccine. Flechtner sees the potential in neoantigen-targeted tumor vaccines to treat cancer patients and has high hopes that the new clinical data will become available soon.

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