What is a Vaccine-Related Sarcoma?

Tumor vaccine is one of the hot topics in recent years. Its principle is to introduce tumor antigens in various forms, such as tumor cells, tumor-related proteins or peptides, and genes expressing tumor antigens, into patients to overcome tumor-induced immunity. Inhibit state, enhance immunogenicity, activate the patient's own immune system, induce body cellular and humoral immune responses, so as to achieve the purpose of controlling or removing tumors.

Tumor vaccine is one of the hot topics in recent years. Its principle is to introduce tumor antigens in various forms, such as tumor cells, tumor-related proteins or peptides, and genes expressing tumor antigens, into patients to overcome tumor-induced immunity. Inhibit state, enhance immunogenicity, activate the patient's own immune system, induce body cellular and humoral immune responses, so as to achieve the purpose of controlling or removing tumors.

Cancer vaccine introduction

Tumor vaccine is one of the hot topics in recent years. Its principle is to introduce tumor antigens in various forms, such as tumor cells, tumor-related proteins or peptides, and genes expressing tumor antigens, into patients to overcome tumor-induced immunity. Inhibit state, enhance immunogenicity, activate the patient's own immune system, induce body cellular and humoral immune responses, so as to achieve the purpose of controlling or removing tumors. ^[1] In April 2010, the US Food and Drug Administration (FDA) approved Provenge / sipuleucel-T for the treatment of advanced prostate cancer, making it the first autologous active immunotherapy drug and the first truly therapeutic cancer Vaccines paved the way for the development of other similar products. ^{[1] [2-3]}

Cancer vaccine development background

Traditional cancer treatment methods, such as surgery, radiation therapy, and medication, all have certain limitations. Due to poor targeting, radiotherapy and drug treatment are prone to damage normal cells and produce adverse reactions. Malignant tumors have biological characteristics that are susceptible to invasion and recurrence, so they need better targeted and less toxic treatments ^[4] . With the development of tumor genomics, biological immunotherapy has become the fourth method of tumor treatment. Studies have shown that tumor cells have tumor antigens, and the immune system can distinguish tumor cells from normal cells by identifying tumor antigens. The tumor vaccine expresses specific and immunogenic tumor antigens (such as peptides, DNA, and RNA), with the help of adjuvants such as cytokines and chemokines, to activate or strengthen the body's own anti-tumor immunity, and then Kills and removes tumor cells ^[5] . At present, tumor vaccines have become a research hotspot in the field of tumor therapy ^[6] .

Cancer vaccine drug classification

At present, tumor vaccines that are on the market and under development can be roughly divided into four categories, namely: whole-cell vaccines, tumor peptide vaccines, genetically engineered vaccines, and antibody tumor vaccines.

1.Whole cell vaccine

Whole cell vaccines can be further divided into tumor cell vaccines and dendritic cell (DC) vaccines according to the source of the cells. When tumor-specific antigens have not been identified, tumor whole-cell vaccines have their unique advantages. The tumor whole cell vaccine contains a full range of tumor-associated antigens (TAA), rich in antigen epitopes of CD ₈ T cells, CD ₄ helper T cells, and can simultaneously express MHC class and restricted antigens, causing a comprehensive and effective antitumor response Induction of long-lasting memory T cells. ^[7]

The traditional method of preparing tumor whole cell vaccines is to use physical, chemical or biological methods (ultraviolet irradiation, heating, neuraminidase, etc.) to treat autologous or allogeneic tumor cells. The vaccine retains immunogenicity but is not tumorigenic . With the development of modern biotechnology, the introduction of target gene fragments into tumor cells has been achieved, such as: MHC-1 molecules, costimulatory cytokines (IL-2, IL-12 and GM-CSF), etc., immunogenicity Further improve. ^[8-9]

DC, as the most powerful full-time APC, is the key to triggering a strong immune response to tumor antigens. However, tumor DCs in tumor hosts have less infiltration and impaired function. Therefore, in vitro cultivation of host DCs bearing tumor antigens to prepare DC tumor vaccines is an effective strategy to obtain a strong immune response in tumor hosts. In April 2010, the US FDA approved sipuleucel-T (Provenge), the first autologous cell immunotherapy drug with DC as the main effector cell. Its indication is asymptomatic or mild symptoms of metastatic castration resistant prostate cancer treatment. ^[10]

2.Peptide vaccine

The preparation of a polypeptide vaccine using an antigen polypeptide eluted from the surface of a tumor cell or a protein abnormally expressed inside the tumor cell has the advantages of strong specificity and high safety. Further modification of amino acid residues, change of amino acid sequence or preparation of heat shock protein-peptide complex can not only effectively improve the specificity of the peptide antigen, but also avoid autoimmunity similar to the host cell. With the discovery of a large number of tumor antigens and peptide epitopes, and the introduction and implementation of corresponding immunization schemes, a variety of tumor peptide vaccines have gradually entered clinical research. Such as the pancreatic cancer vaccine GV1001 ^[11] developed by the Korean company KAEL-Gem Vax, Cervarix ^[12] , a bivalent cervical cancer vaccine developed by GlaxoSmithKline (GSK). In addition, some new-generation tumor peptide vaccines have appeared in the past 5 years. Among them, long peptide vaccines are different from classic peptide vaccines containing only one or several epitopes, and multivalent long peptide vaccines contain several human leukocyte antigens (HLA). Type-restricted molecules can cause both CTL and T helper cell effects ^[13] .

Genetically engineered vaccines

The gene encoding tumor-specific antigen is loaded into a recombinant virus vector or plasmid DNA using genetic engineering technology and directly injected into the human body. With the aid of the vector itself or the human gene expression system, specific humoral and cellular immunity can be continuously caused. This is an unmatched advantage of genetic engineering vaccines over other tumor vaccines, and thus has become a hot spot in tumor biotherapy research. Studies have shown that fusing DNA encoding cytokines and bacterial proteins with plasmid DNA of genetically engineered vaccines can effectively improve their immunogenicity and cause a strong immune response ^[14-15] .

4, antibody tumor vaccine

The monoclonal antibody tumor vaccine designed based on the theory of antibody-dependent cell-mediated cytotoxicity (ADCC) is a new direction for vaccine development. Monoclonal antibodies can bind to specific antigens with high specificity and have good molecular targeting functions. At present, there are two types of monoclonal antitumor drugs: one is an antitumor monoclonal antibody; the other is an antitumor monoclonal antibody conjugate, or immunoconjugate. Monoclonal antibody drugs combine with tumor antigens to stimulate DCs and stimulate the action of CD ₈ T cells. This technology has made significant progress in the treatment of melanoma and breast cancer. The FDA approved Bristol-Myers Squibb's YERVOY monotherapy in March 2011 for the treatment of patients with inoperable resection or metastatic melanoma ^[16] . In addition, the antitumor monoclonal antibody Trastuzumab (Herceptin) has a good therapeutic effect on human HER-2 positive metastatic breast cancer ^[17] .

Cancer vaccine application prospects

Cancer vaccine research has made great progress in recent years, and its clinical application effect has also improved. Cancer vaccines have evolved from early non-specific vaccines to today s tumor antigen-specific vaccines, from vaccines based on genetically modified tumor cells in the early 1990s to tumor antigen-specific vaccines based on dendritic cells, All are closely related to the development of molecular biology, immunology and gene transfer technology. However, in the past, there was a phenomenon of high expectations for tumor vaccines. The treatment of tumors by tumor vaccines is only one of the types of tumor specific active immunotherapy, which belongs to the category of tumor biological therapy. At this stage, we cannot expect to cure advanced tumors with this therapy alone. How to combine active specific immunotherapy with surgery, chemotherapy, and radiation therapy to give full play to the advantages of comprehensive treatment will become an important research direction.