In cancer immunotherapy, cytotoxic T lymphocytes (CTLs) serve as the key players in targeting and destroying cancer cells. The identifiers they rely on to differentiate healthy cells from malignant ones are known as antigens. To harness this mechanism, we are developing cancer peptide vaccines, which utilize peptides short fragments of proteins as cancer-specific antigens.

The cancer peptide vaccine we are developing functions by delivering cancer antigen peptides that stimulate cytotoxic T lymphocytes (CTLs), a crucial component of the immune system. Once activated, CTLs recognize cancer-specific antigens displayed on the surface of tumor cells and subsequently eliminate those cancer cells.

Unlike B cells and antibodies, T cells cannot directly detect free protein molecules. Instead, they recognize peptides presented on the cell surface as complexes of intracellularly processed low-molecular-weight antigen fragments bound to HLA (human leukocyte antigen) molecules. The specific regions of these antigens, known as T cell epitopes, are determined by intracellular processing and HLA binding affinity rather than the protein’s higher-order structure. Due to HLA polymorphism, different HLA types present distinct T cell epitopes.

Cancer antigens originate from endogenous proteins synthesized within tumor cells and are primarily recognized by CD8+ cytotoxic T lymphocytes (CTLs). Proteins produced in cancer cells undergo ubiquitination and are degraded by the proteasome into short peptides, typically 8–10 amino acids in length. These peptides are transported to the endoplasmic reticulum (ER), where those capable of binding HLA class I molecules form peptide-HLA complexes that are expressed on the cell surface. CTLs identify and bind to these complexes through their T cell receptors.

Because cancer cells proliferate rapidly, they display high levels of peptides derived from proliferation-associated proteins on their surfaces. Additionally, cancer-specific peptides, or tumor markers, are expressed on tumor cells and serve as targets for CTL-mediated recognition and destruction.

Cancer peptide vaccines exploit this mechanism by chemically synthesizing peptides identical to those naturally expressed on cancer cell surfaces. When administered to patients, these synthetic peptides are captured by local antigen-presenting cells (APCs), such as dendritic cells and macrophages, and form peptide-HLA class I complexes. APCs then migrate to nearby lymph nodes, where they present the peptide to CTL precursors. These precursors become activated, proliferate, and differentiate into mature CTLs. The CTLs then travel via the lymphatic system to the tumor site, recognize cancer cells presenting the same peptide-HLA complexes, and induce apoptosis in the targeted cancer cells.