Neoantigens are unique markers that appear on the surface of abnormal cells, distinguishing them from healthy ones. Their presence serves as a signal, potentially allowing the body’s natural defense systems to identify and respond to these aberrant cells.
How Neoantigens Form
Neoantigens originate from genetic changes within tumor cells. Cancer cells accumulate DNA mutations, such as single nucleotide variations, insertions, or deletions. These “typos” lead to the production of altered proteins that are not typically found in the body.
These altered proteins are processed inside cancer cells. Small fragments, or peptides, are then presented on the cell’s surface by major histocompatibility complex (MHC) molecules. This presentation makes neoantigens visible to the immune system. As they arise from tumor-specific mutations and are absent from normal tissues, they represent distinct targets.
Why Neoantigens Are Important
Neoantigens hold significant importance because they are recognized as “foreign” by the immune system, unlike normal self-antigens that the immune system typically tolerates. This foreign nature means they are highly immunogenic, capable of triggering a strong immune response. Specifically, immune cells known as T cells can identify these newly formed protein fragments as abnormal and target the cancer cells displaying them. The ability of T cells to recognize neoantigens is a crucial step in the body’s anti-tumor response.
This unique recognition allows the immune system to distinguish cancer cells from healthy cells with precision. Because neoantigens are entirely unique to cancer cells, targeting them carries a lower risk of inadvertently harming healthy tissues, a significant advantage over other forms of cancer treatment. While a large number of candidate neoantigens might be present, only a small fraction often elicits a strong T cell response, influencing their potential as effective targets. This specificity makes neoantigens a focal point for developing targeted cancer therapies.
Neoantigens in Cancer Treatment
The unique characteristics of neoantigens are being harnessed in several innovative cancer therapies, offering personalized approaches to treatment. One primary method involves neoantigen vaccines, which are designed to train the patient’s immune system to specifically attack cancer cells. This process begins with identifying the specific genetic mutations within an individual patient’s tumor through advanced sequencing technologies. Based on these identified mutations, patient-specific neoantigens are predicted and then synthesized.
These synthesized neoantigens are then used to create a personalized vaccine, which is administered to the patient. The vaccine aims to activate antigen-presenting cells, such as dendritic cells, which then present the neoantigens to T cells. This exposure primes and activates T cells, encouraging them to recognize and eliminate cancer cells that express those particular neoantigens. This approach seeks to generate a robust and long-lasting immune response against the tumor.
Another therapeutic strategy leveraging neoantigens involves immune checkpoint inhibitors. These therapies work by “releasing the brakes” on the immune system, allowing existing T cells to more effectively attack cancer. Immune checkpoint inhibitors, such as those targeting PD-1/PD-L1 or CTLA-4, reactivate T cells that may have been suppressed by the tumor. The effectiveness of these therapies is closely linked to the presence of neoantigens, as they provide the specific targets for these reactivated T cells. Tumors with a higher number of mutations, and consequently more neoantigens, often show a better response to immune checkpoint blockade because there are more distinct targets for the immune system to recognize.