Tumor/Cancer vaccines - Examples of vaccines against tumor

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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].

Table 12. Examples of vaccines against tumor
		Vaccine classification
Prostate cancer	PAP	DNA vaccine	Intravenous	Phase III	Improved survival	[167]
Prostate cancer	VEGF Receptor 2	DNA vaccine	Oral	Phase I	Vaccine were well-tolerated and T effector was increased	[168]
NSCLC	MUC1	Protein/peptide-based vaccines	Intravenous	Phase III	Tecemotide might have some adverse events on patients who initially receive concurrent chemoradiotherapy	[169]
NSCLC	MUC1	Protein/peptide-based vaccines	Subcutaneous	Phase III	Safe, but adverse events existed	[170]
Melanoma	HSPPC-96	Protein/peptide-based vaccines	Intradermal	Phase I/II	Feasible and safe. Modest immune response and anti-tumor activity were observed	[171]
Ovarian carcinoma, glioblastoma, pancreatic carcinoma, stomach carcinoma	Multiple tumor-associated antigens (TAAs)	Tumor cell vaccine	Intradermal	Phase I/II	Antitumor immune memory and patient survival were improved	[172]
Prostate cancer	PAP	Recombinant adenoviral vector-based vaccine	Subcutaneous	Phase I/II	Safe with no serious vaccine-related adverse events, and anti-PSA T-cell responses were induced	[172]
Melanoma	IL-2	Autologous tumor cell vaccine via Ad vector-mediated IL-2 transfection	Intradermal/subcutaneous	Phase I	Safe and tolerate	[173]
Melanoma	MART-1 or gp100	Recombinant adenoviral vector-based vaccine	Intramuscular/subcutaneous	Phase I	Safe, but presenting high levels of neutralizing antibody.	[174]
Melanoma	GM-CSF	Irradiated autologous tumor cell vaccine via Ad vector-mediated GM-CSF transfection	Intradermal/subcutaneous	Phase I	Well tolerated and induce anti-tumor immune response	[175]
Melanoma	MART-1	Autologous dendritic cell vaccine via Ad vector-mediated MART-1 transfection	Intradermal	Phase I/II	Safe and immunogenic	[176]
Solid tumor	HER2	DNA vaccine and adenoviral vector-based vaccine	Intramuscular	Phase I	Well tolerated and without any serious adverse events	[79]
Non-muscle-invasive bladder cancer (NMIBC)	IFNα/Syn3	Recombinant adenoviral vector-based vaccine	Intravesical	Phase II	Well tolerated	[177]
Non-muscle-invasive bladder cancer (NMIBC)	IFNα2b/Syn4	Recombinant adenoviral vector-based vaccine	Intravesical	Phase Ib	Promising drug efficacy was shown	[178]
Non-muscle-invasive bladder cancer (NMIBC)	IFNα/Syn3	Recombinant adenoviral vector-based vaccine	Intravesical	Phase I	Well tolerated with no dose limiting toxicity	[179]
Colorectal cancer	CEA	Recombinant adenoviral vector-based vaccine	Subcutaneous	Phase I/II	Safe and immunogenic	[179]
Colorectal cancer	CEA	Recombinant adenoviral vector-based vaccine	Subcutaneous	Phase I	Minimal toxicity	[180]
Hepatocellular cancer	AFP	DNA vaccine and adenoviral vector-based vaccine	Intramuscular	Phase I	Safe and immunogenic	[181]
B-cell lymphosarcoma	Telomerase	Recombinant adenoviral vector-based vaccine	In femoral biceps	Phase I	Safe 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].

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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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Collection of COVID-19 landscape knowledge base

COVID-19 landscape Knowledge Base

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8. References

Collection of COVID-19 landscape knowledge base

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