Tumor/Cancer vaccines – Examples of vaccines against tumor

Tumor/Cancer vaccines

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Despite several decades’ continuous efforts on tumor therapy with radiation treatment and chemotherapy, serious adverse effects, including nausea, vomiting, physical weakness, mental malaise, sweating, decreased white blood cells and platelets, are really painful and intolerable. Tumor vaccines are vaccines using tumor-specific antigens (TSAs) to provoke the host immune system to specifically eliminate and suppress tumors or cancers, exhibiting promising advantages over traditional radiation and chemotherapy. Several kinds of tumor vaccines are developed for the therapy of tumor as shown in Fig. 18 [164], including nucleic acid vaccines (DNA vaccines and RNA vaccines), protein/peptide vaccines, and cell-based vaccines with tumor antigens.

Figure. 18 Schematic representation of tumor (cancer) vaccines [164].

Nucleic acid-based vaccines can be taken up by APCs and translated into specific antigen to provoke host immune system, such as Tyrosinase Related Protein 1 (TYRP1/gp75) vaccine for the treatment of melanoma [165]. Protein/peptide-based vaccines are tumor specific antigens protein or epitope, which can directly stimulate immune system, such as HSPPC-96 vaccine (Oncophage) for the treatment of melanoma, gastric cancer, renal cell cancer, lymphoma, and pancreatic cancer [166]. Cell-based vaccines are autologous dendritic cells or other immune cells with insertion of tumor antigen genes or transfected with tumor antigens or peptides, such as dendritic cell vaccine, provenge (sipuleucel-T), targeting PAP for the therapy of prostate cancer [167]. A large number of tumor vaccines have been translated into clinics and encouraging therapy outcomes have been achieved (Table 11).

Table 11. Examples of vaccines against tumor
Disease Antigen/target
Vaccine classification

Delivery route Status Outcome References
Prostate cancerPAPDNA vaccineIntravenousPhase IIIImproved survival[167]
Prostate cancerVEGF Receptor 2DNA vaccineOralPhase IVaccine were well-tolerated and T effector was increased[168]
NSCLCMUC1Protein/peptide-based vaccinesIntravenousPhase IIITecemotide might have some adverse events on patients who initially receive concurrent chemoradiotherapy[169]
NSCLCMUC1Protein/peptide-based vaccinesSubcutaneousPhase IIISafe, but adverse events existed[170]
MelanomaHSPPC-96Protein/peptide-based vaccinesIntradermalPhase I/IIFeasible and safe. Modest immune response and anti-tumor activity were observed[171]
Ovarian carcinoma, glioblastoma, pancreatic carcinoma, stomach carcinomaMultiple tumor-associated antigens (TAAs)Tumor cell vaccineIntradermalPhase I/IIAntitumor immune memory and patient survival were improved[172]
Prostate cancerPAPRecombinant adenoviral vector-based vaccineSubcutaneousPhase I/IISafe with no serious vaccine-related adverse events, and anti-PSA T-cell responses were induced[172]
MelanomaIL-2Autologous tumor cell vaccine via Ad vector-mediated IL-2 transfectionIntradermal/subcutaneousPhase ISafe and tolerate[173]
MelanomaMART-1 or gp100Recombinant adenoviral vector-based vaccineIntramuscular/subcutaneousPhase ISafe, but presenting high levels of neutralizing antibody.[174]
MelanomaGM-CSFIrradiated autologous tumor cell vaccine via Ad vector-mediated GM-CSF transfectionIntradermal/subcutaneousPhase IWell tolerated and induce anti-tumor immune response[175]
MelanomaMART-1Autologous dendritic cell vaccine via Ad vector-mediated MART-1 transfectionIntradermalPhase I/IISafe and immunogenic[176]
Solid tumorHER2DNA vaccine and adenoviral vector-based vaccineIntramuscularPhase IWell tolerated and without any serious adverse events[79]
Non-muscle-invasive bladder cancer (NMIBC)IFNα/Syn3Recombinant adenoviral vector-based vaccineIntravesicalPhase IIWell tolerated[177]
Non-muscle-invasive bladder cancer (NMIBC)IFNα2b/Syn4Recombinant adenoviral vector-based vaccineIntravesicalPhase IbPromising drug efficacy was shown[178]
Non-muscle-invasive bladder cancer (NMIBC)IFNα/Syn3Recombinant adenoviral vector-based vaccineIntravesicalPhase IWell tolerated with no dose limiting toxicity[179]
Colorectal cancerCEARecombinant adenoviral vector-based vaccineSubcutaneousPhase I/IISafe and immunogenic[179]
Colorectal cancerCEARecombinant adenoviral vector-based vaccineSubcutaneousPhase IMinimal toxicity[180]
Hepatocellular cancerAFPDNA vaccine and adenoviral vector-based vaccineIntramuscularPhase ISafe and immunogenic[181]
B-cell lymphosarcoma TelomeraseRecombinant adenoviral vector-based vaccineIn femoral bicepsPhase ISafe and prolong the survival time[182]

As is known to all, there are many somatic mutations in tumors varying in different individuals, and more and more highly heterogeneous neoantigens are discovered and identified through next generation sequencing (NGS) technologies. On the basis of tumor mutation profiles, personalized cancer vaccines are designed and developed to activate immune system against cancer by targeting specific epitopes of neoantigens (Fig. 19). Once delivered into the body with adjuvant, personal vaccines provokes host immune responses through the following processes:

① Neoantigen-specific peptides inside personal vaccines are captured and processed by APCs;
② Activated APCs migrate to lymph nodes and present neoantigens to T cells with MHC molecules;
③ Neoantigens are recognized and bound by T cell receptor, thus priming and activating cell immunity;
④ Neoantigen-specific T cells are expanded, migrate and infiltrate to tumor microenvironment;
⑤ Neoantigen-specific T cells kill tumor cells with neoantigens, leading to the release of more antigens, which elicits adaptive immune memory and augments the immune responses.

So far, personal vaccines have achieved encouraging anti-tumor effects in the pre-clinical studies with mouse models and clinical trials. For example, using whole-exome and transcriptome sequencing and mass spectrometry analysis, more than 1300 amino acid changes were identified in MC-38 and TRAMP-C1 murine tumor models, and vaccination with mutated peptides exhibits remarkable and sustainable inhibition of tumor growth [183]. For human melanoma therapy, a neoantigen was discovered via whole exome sequencing and HLA binding prediction algorithm, and dendritic cell vaccine with the neoantigen significantly enhances the T cell immune response to the neoantigen in some patients [184].

Figure 19. Schematic of strategies and principles of personal neoantigen vaccines [164]. (I) Get the tumor specimen from patient and extract the DNA. (II) Characterize the non-synonymous mutations via NGS. (III) Prepare the personal neoantigen vaccine in vitro and deliver the vaccine to patients with adjuvant.

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