Immunotherapy Strategies for Tumor Antigens

Immunotherapy for cancer harnesses the immune system to recognise and eradicate malignant cells by targeting tumour antigens—molecules selectively expressed or overexpressed by tumours. Strategies range from vaccination platforms that deliver defined peptide, protein, RNA or DNA antigens to dendritic-cell-based or viral and bacterial vector systems, to adoptive cell therapies employing T cells engineered with receptors specific for tumour epitopes. Checkpoint blockade antibodies directed at inhibitory receptors on T cells reinvigorate antitumour responses, often in combination with vaccines or adoptive transfers. Emerging approaches include modulation of antigen presentation through epigenetic drugs, delivery of novel adjuvants to amplify immunity, and combination regimens that synchronise innate and adaptive effectors. These tactics aim to overcome central and peripheral tolerance, antigen heterogeneity and the immunosuppressive tumour microenvironment. By integrating biomarkers and personalised antigen selection, contemporary immunotherapy strives to maximise specificity and durability of response, offering a global impact in the treatment of solid and haematological malignancies.

Research from Nature Portfolio

A recent phase 1/2 study evaluated an immune-modulatory vaccine targeting indoleamine 2,3-dioxygenase (IDO) and PD-L1 administered alongside anti-PD-1 therapy in patients with metastatic melanoma. The combination demonstrated a high objective response rate of 80 %, including complete remissions in nearly half of participants, with a median progression-free survival exceeding two years. Vaccine-specific CD4+ and CD8+ T cells reactive to IDO and PD-L1 antigens were detected in over 90 % of vaccinated patients, and expanded clones were observed infiltrating tumour sites. This proof-of-concept trial highlights the clinical potential of vaccines directed against tumour-expressed immunosuppressive molecules when integrated with checkpoint blockade.

Immunotherapy Strategies for Tumor Antigens publication trend

The graph below shows the total number of articles in immunotherapy strategies for tumor antigens across all publications each year (not limited to Nature Index journals).

Technical terms

Tumour-associated antigen (TAA): A molecule expressed predominantly by tumour cells and recognised by the immune system.

Cancer-testis antigen (CTA): A subset of TAAs normally restricted to germ cells but aberrantly expressed in tumours.

Immune checkpoint: Regulatory receptor–ligand interactions that modulate T-cell activation and maintain self-tolerance.

Adoptive cell therapy: Transfer of autologous or allogeneic immune cells engineered or expanded to target tumour epitopes.

Epitope: The specific peptide fragment of an antigen recognised by T-cell receptors or antibodies.

References

1. A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma. Nature Medicine (2021).
2. NY‐ESO‐1 antigen: A promising frontier in cancer immunotherapy. Clinical and Translational Medicine (2024).
3. Recombinant single-cycle influenza virus with exchangeable pseudotypes allows repeated immunization to augment anti-tumour immunity with immune checkpoint inhibitors. eLife (2023).
4. Current advances in cancer vaccines targeting NY-ESO-1 for solid cancer treatment. Frontiers in Immunology (2023).