Challenges towards the realization of individualized cancer vaccines

  title={Challenges towards the realization of individualized cancer vaccines},
  author={{\"O}zlem T{\"u}reci and Martin L{\"o}wer and Barbara Schr{\"o}rs and Maren Lang and Arbel D. Tadmor and Uğur Şahin},
  journal={Nature Biomedical Engineering},
Bringing truly personalized cancer vaccination with tumour neoantigens to the clinic will require overcoming the challenges of optimized vaccine design, manufacturing and affordability, and identification of the most suitable clinical setting. 

Targeting public neoantigens for cancer immunotherapy.

The opportunities and challenges involved in the identification of suitable public neoantigen targets and the development of therapeutic agents targeting them are reviewed.

Advances in the development of personalized neoantigen-based therapeutic cancer vaccines

An overview of the complex process that is necessary to generate a personalized neoantigen vaccine, the types of vaccine-induced T cells that are found within tumours and outline strategies to enhance the T cell responses are provided.

Recent Advances in Polymeric Nanomedicines for Cancer Immunotherapy

In this review, recent advances in polymeric nanomedicines for cancer immunotherapy are highlighted and thoroughly discussed in terms of 1) antigen presentation, 2) activation of antigen‐presenting cells and T cells, and 3) promotion of effector cells.

Personalized Cancer Vaccines: Clinical Landscape, Challenges, and Opportunities.

Neoantigen: A New Breakthrough in Tumor Immunotherapy

The latest advances in the classification of immunotherapy and the process of classification, identification and synthesis of tumor-specific neoantigens, as well as their role in current cancer immunotherapy are summarized.

Post translational modification-assisted cancer immunotherapy for effective breast cancer treatment†

Titanium modified dendritic mesoporous silica nanoparticles are applied to assist the specific enrichment of phosphorylated tumor antigens released upon immunogenic cell death and significantly improved the tumor inhibition efficacy in a bilateral breast cancer model.

Co-Delivery of Peptide Neoantigens and Stimulator of Interferon Genes (STING) Agonists Enhances Response to Cancer Vaccines.

Therapeutic immunization with nanoSTING-vax, in combination with immune checkpoint blockade, inhibited tumor growth in multiple murine tumor models, even leading to complete tumor rejection and generation of durable antitumor immune memory.

Engineering Magnetosomes for High-Performance Cancer Vaccination

A cancer-derived magnetosome with the integration of various recent nanotechnologies successfully demonstrates its promise for safe and high-performance cancer vaccination.

Cationic Nanoparticle-Based Cancer Vaccines

Different cationic nanoparticulate vaccines, molecular mechanisms of adjuvanticity and biodistribution profiles upon administration via different routes are discussed, and the perspectives of cationo-pharmaceuticals for improving immunotherapy of cancer are discussed.



Targeting the tumor mutanome for personalized vaccination therapy

Next generation sequencing enables identification of immunogenic tumor mutations targetable by individualized vaccines. In the B16F10 melanoma system as pre-clinical proof-of-concept model, we found

Evolving synergistic combinations of targeted immunotherapies to combat cancer

Progress in the synergistic design of immune-targeting combination therapies is discussed and the challenges involved in tailoring such strategies to provide maximal benefit to patients are highlighted.

The future of immune checkpoint therapy

The way forward for this class of novel agents lies in the ability to understand human immune responses in the tumor microenvironment, which will provide valuable information regarding the dynamic nature of the immune response and regulation of additional pathways that will need to be targeted through combination therapies to provide survival benefit for greater numbers of patients.

Neoantigens in cancer immunotherapy

Observations indicate that neoantigen load may form a biomarker in cancer immunotherapy and provide an incentive for the development of novel therapeutic approaches that selectively enhance T cell reactivity against this class of antigens.

Elements of cancer immunity and the cancer–immune set point

Clinical studies are beginning to define these factors as immune profiles that can predict responses to immunotherapy, suggesting that a broader view of cancer immunity is required.

Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer

The first-in-human application of individualized mutanome vaccines in melanoma is reported, demonstrating that individual mutations can be exploited and opening a path to personalized immunotherapy for patients with cancer.

Targeting the Heterogeneity of Cancer with Individualized Neoepitope Vaccines

How to transform tumor mutanome data to actionable knowledge for tailoring individualized vaccines “on demand” has become a novel research field with paradigm-shifting potential.

A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells

The results demonstrate that vaccination directed at tumor-encoded amino acid substitutions broadens the antigenic breadth and clonal diversity of antitumor immunity.

Checkpoint Blockade Cancer Immunotherapy Targets Tumour-Specific Mutant Antigens

Tumour-specific mutant proteins are identified as a major class of T-cell rejection antigens following anti-PD-1 and/or anti-CTLA-4 therapy of mice bearing progressively growing sarcomas, and it is shown that therapeutic synthetic long-peptide vaccines incorporating these mutant epitopes induce tumour rejection comparably to checkpoint blockade immunotherapy.

Mutant MHC class II epitopes drive therapeutic immune responses to cancer

The tailored immunotherapy approach introduced here may be regarded as a universally applicable blueprint for comprehensive exploitation of the substantial neo-epitope target repertoire of cancers, enabling the effective targeting of every patient’s tumour with vaccines produced ‘just in time’.