Neoantigen of tumor

Introduction of Neoantigen immunotherapy

Neoantigen is a new antigen encoded by mutated genes of tumor cells, which is mainly produced by point mutation, deletion mutation, gene fusion and other new abnormal proteins that are different from proteins expressed by normal cells.The peptide fragments formed after enzymatic hydrolysis of these proteins are presented to T cells as antigens through DC cells, which can promote T cells to become mature and activated T cells that can specifically recognize tumor neoantigens, and make the number of activated T cells proliferate.Using the immune activity of tumor neoantigen, people can design and synthesize neoantigen vaccine according to the mutation of tumor cells, so as to immunize patients and achieve therapeutic effect.

I. The design process of neoantigen immunotherapy

As shown in the figure below, the process design of neoantigen immunotherapy is roughly as follows:

1) Obtain tumor DNA

2) Whole exon sequencing of tumor cells

3) The somatic mutations of tumor cells were analyzed and the HLA-bound mutant neoantigens were calculated

4) Synthesize neoantigen and conduct immunization

5) Detect whether the number of T cells with specific binding neoantigen is increased

The design process of neoantigen immunotherapy

II.The design process of neoantigen immunotherapy 

Second, the way of neoantigen vaccine.There are various methods of neoantigen vaccine, including: neoantigen DC cell vaccine, neoantigen peptide vaccine, neoantigen DNA vaccine, RNA vaccine and so on.Neoantigen vaccines

The design process of neoantigen immunotherapy

(1) Neoantigen DC vaccine treatment process

The neoantigen was co-cultured with DC cells, and then implanted into the body to activate CD8+T cells. The specific process is shown in the figure below.

(2) Neoantigen peptide vaccine

Immunization by direct injection of neoantigen peptides and adjuvants under the skin has been successful in the treatment of melanoma and breast cancer.The specific action process is shown in the figure below:Neoantigen peptide vaccine

Neoantigen peptide vaccine

(3) Neoantigen DNA/RNA vaccine

DNA vaccine is a vector that translocates neoantigen-coding DNA into tumor cells to make them express neoantigens in large quantities, so as to activate cellular immunity.RNA vaccines deliver RNA directly to tumor cells.Neoantigen DNA/RNA vaccine

Neoantigen DNA/RNA vaccine

III. Several key steps of neoantigen immunotherapy

(1) Accurate sequencing and accurate design, which must rely on the continuous optimization of the algorithm, including HLA typing, the calculation of the binding force between neoantigen and MHC, TCR analysis and other contents.

(2) Break through the barrier and submit successfully.

(3) excitable T cells (neoantigen-specific CTL) can accurately assemble in tumor tissues

(4) The inhibitory factors of T cells should be removed

Several key steps of neoantigen immunotherapy

Several key steps of neoantigen immunotherapy

Therefore, neoantigen immunotherapy still has many links to be further optimized and improved.

In any case, tumor neoantigens provide patients with a new immunotherapy method, which has the advantages of less side effects, multiple targets, no cancer restrictions, and immune memory. There will be tumor neoantigens therapy on the market in the near future, which will benefit the majority of patients.

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