Personalized Neoantigen Cancer Vaccine

Cancer is a serious threat to human health and because of its rapid development and swift transmissibility, it is usually difficult to treat once it is discovered. At the same time, different individuals' different manifestations and responses to the same type of tumor make treatment for a particular type of tumor likely to be ineffective for some patients, which also increases the difficulty of cancer treatment. The discovery of neoantigen brings hope to the preparation of individualized vaccines. Creative Biolabs has extensive experience in oncology vaccine research and we have a wealth of strategies and services to meet your needs in cancer vaccine research.

Background

Research on the use of the immune system against malignant tumors has been around for decades, and as of now, there has been a revolutionary breakthrough in understanding this aspect. In addition to the emergence of immune checkpoint inhibitors and CAR-T therapies, advances in genomics technology and bioinformatics have also made neoantigens a highly promising target for designing tumor vaccines since accumulation of a large number of genetic alterations is a major feature of cancer, while tumor-specific neoepitopes produced by somatic mutations can be recognized as foreign substances by T cells of the organism. The concept of cancer immunotherapy dates back to the late 1800s, and Coley believes that inoculating inactivated toxins can stimulate the body's immune system and affect cancer (this is also the current treatment for bladder cancer), and in the early 1900s, immune system is believed to be able to clear cancer cells and this view was extended in the 1950s to immune surveillance theory that lymphocytes can recognize malignant cells. Thereafter, at the 1960s, the doctrine that tumor-associated antigens were able to reject tumors appeared. Based on the above theory and the latest research, two prophylactic cancer vaccines and one therapeutic cancer vaccine have recently received FDA approval.

Cancer Immunology

An in-depth understanding of cancer immunology is the theoretical basis for the design of a successful neoantigen vaccine. First, tumor cells can release tumor-specific antigens and these antigens are then taken up by antigen presenting cells like dendritic cells, where the ingested antigens are degraded into small peptides by proteases or peptidases. These peptides are further transported into the endoplasmic reticulum. In the endoplasmic reticulum, such peptides will localize and bind to MHC molecules. The peptide-MHC complex is thereafter transported to the cell surface via the Golgi after formation. The dendritic cells carrying the antigen migrate to the lymph nodes where they will trigger and activate T cells that recognize the antigen present on the surface of the dendritic cells. The T cell receptor of CD8+ T cells correctly recognizes peptides bound to MHC class I molecules on the surface of dendritic cells, and the interaction between T cells and antigen presenting cell through surface proteins including CD80/86 and CD28 is essential for activation of CD8+ T cells. After the dendritic cells release the cytokines required for activation of T cells, the activated T cells proliferate in a large amount, metastasize to the tumor site, and infiltrate the tumor cells. Once identified the antigen presented by the antigen presenting cells, the T cells will kill these tumor cells.

A schematic of the cancer immunology. - Creative Biolabs

Fig.1 A schematic of the cancer immunology.

Neoantigen Vaccine

There have been a variety of individualized cancer vaccine strategies in history, including whole tumor cells, T cells, viral vectors, DNA, RNA, dendritic cells, proteins and peptides, all of which have varying degrees of restriction, while peptide vaccine has become a hot spot for the development of individualized tumor vaccines due to its advantages of simplicity of production, low cost, ability to accommodate multiple antigen sequences and easy monitoring of the vaccine's immune effect. Among the peptide-based tumor vaccines, two types of vaccines that target non-mutated tumor-associated antigens and mutant antigens present only in tumor cells are included. The former is also present in the genome of normal cells. In general, their expression is low but they will be overexpressed when the cells become cancerous. These antigens are also called self-antigens like NY-ESO-1, gp100, MAGE-A3, Her2/Neu, and the like that have been identified. Since such antigens are also present in normal tissues, there may be a possibility of tolerance or autoimmunity. Unlike self-antigens, neoantigens use mutant peptides as antigens. Such antigenic sequences are only present in tumor cells, so there are no central tolerance and autoimmunity concerns. Such tumor-specific antigens can be derived from post-translational modifications, viral proteins, and somatic mutations. Neoantigens also includes both shared and personalized types, the former of which are co-existing in certain types of tumors or in patients, and such antigens can be used as vaccines to treat the same type of cancer. It is well known that even the same type of tumor varies widely depending on the specific circumstances of each individual, so fully individualized therapy is the best way for each cancer patient. Personalized neoantigen vaccine is the best option to realize this objective.

The preparation process of personalized neoantigen vaccine includes: 1) extracting tumor biopsies from the patient, then sequencing the DNA/RNA exome and analyzing the data by computer program to determine mutanome; 2) using predictive algorithm to screen mutations obtained from sequencing to determine the most immunogenic antigens; 3) artificially synthesizing possible peptides elucidated by the algorithms and assessing their affinity for binding to the corresponding HLA; 4) peptide manufacturing and purification as well as formulation. The correct prediction and selection of epitopes are crucial to the successful design of individualized cancer vaccines throughout the preparation.

Workflow of the personalized neoantigen peptide vaccine. - Creative Biolabs

Fig.2 Workflow of the personalized neoantigen peptide vaccine.

Our Services in Development of Neoantigen Vaccine

  • Next-generation sequencing
  • Accurate neoepitope predicting
  • Advanced scalable peptide synthesizing
  • Affinity evaluation of candidate neoantigen vaccines
  • Complete purification and formulation optimization

The treatment of cancer has always been the focus of researchers. The concept of individualized therapy is a promising strategy for conquering cancer, and the neoantigen vaccine is a representative solution. Creative Biolabs applies its extensive experience in vaccine research to the development of cancer vaccines and has established a systematic neoantigen vaccine development service system to provide the most comprehensive and reliable technical support for cancer vaccine researchers worldwide.


Our services are for research use only. We do not provide services directly to individuals.

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