Cancer Immunotherapy with Peptide Vaccines

Cancer immunotherapy with peptide vaccines harnesses tumour-specific antigens composed of short amino acid sequences to elicit targeted T-cell responses. Unlike whole-cell or viral-vector vaccines, peptide formulations permit precise antigen selection, minimising off-target effects and facilitating standardised manufacturing. Vaccines may include peptides derived from shared tumour-associated antigens or patient-specific neoantigens arising from somatic mutations. Delivery often involves adjuvants or carrier systems to stimulate dendritic cell activation and promote antigen presentation via human leukocyte antigen molecules. Strategies incorporate both CD8+ cytotoxic T-cell epitopes and CD4+ helper epitopes to generate potent and durable immune memory. Recent advances focus on optimising peptide length, sequence-selection algorithms, adjuvant combinations and delivery platforms, including emulsions, nanoparticles and novel toll-like receptor ligands. Integration with checkpoint blockade and conventional therapies has yielded synergistic antitumour effects. Clinical trials in melanoma, hepatocellular carcinoma and other solid tumours demonstrate the capacity of peptide vaccines to induce multifunctional T-cell responses, modulate the tumour microenvironment and achieve prolonged disease control with low toxicity profiles. The global importance of this modality lies in its adaptability to personalised immunotherapy and its potential application across diverse cancer types.

Research from Nature Portfolio

Recent studies in melanoma have examined multipeptide formulations targeting both CD8+ cytotoxic epitopes and CD4+ helper epitopes combined with low-dose cyclophosphamide. Data indicate that inclusion of cognate helper peptides enhances overall survival in specific patient subgroups and potentiates cytotoxic responses, underscoring the importance of T-cell help in vaccine efficacy. In fibrolamellar hepatocellular carcinoma, identification of HLA-presented neoantigens derived from a disease-specific fusion protein enabled the design of a bespoke peptide vaccine. Vaccination elicited multifunctional CD8+ and TH1-polarised CD4+ T-cell responses, with durable relapse-free survival observed in a patient receiving adjuvant polymerase-inhibitor therapy. These findings validate the feasibility of targeting oncogenic driver neoepitopes and highlight the interplay between personalised antigen selection and clinical outcome.

Cancer Immunotherapy with Peptide Vaccines publication trend

The graph below shows the total number of articles in cancer immunotherapy with peptide vaccines across all publications each year (not limited to Nature Index journals).

Technical terms

Peptide vaccine: A formulation of short amino acid sequences derived from tumour antigens designed to elicit specific T-cell responses.

Adjuvant: A substance added to a vaccine to enhance the immune response by activating innate immune pathways.

Neoantigen: A novel peptide antigen arising from tumour-specific mutations, not present in normal tissues.

HLA (human leukocyte antigen): Cell-surface proteins that present peptide antigens to T cells, determining immune recognition.

CD8+ T cell: A cytotoxic lymphocyte subtype that recognises HLA class I-presented peptides and kills antigen-bearing cells.

CD4+ T cell: A helper lymphocyte subtype that recognises HLA class II-presented peptides and supports cytotoxic and humoral responses.

References

1. Multipeptide vaccines for melanoma in the adjuvant setting: long-term survival outcomes and post-hoc analysis of a randomized phase II trial. Nature Communications (2024).
2. The Peptide Vaccine of the Future. Molecular & Cellular Proteomics (2021).
3. A multipeptide vaccine plus toll-like receptor agonists LPS or polyICLC in combination with incomplete Freund’s adjuvant in melanoma patients. Journal for ImmunoTherapy of Cancer (2019).
4. A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer. Journal for ImmunoTherapy of Cancer (2019).
5. The oncogenic fusion protein DNAJB1-PRKACA can be specifically targeted by peptide-based immunotherapy in fibrolamellar hepatocellular carcinoma. Nature Communications (2022).