Table 1:

VBP modifications to enhance antitumor mechanisms

Therapy	Class	Modification	Mechanism	Representative References
Oncolysis	Drug/toxin	Doxorubicin	Intercalates into DNA causing strand breakage and inhibits topoisomerase II, inducing apoptosis	[136,141–145]
		Saporin	Ribosome-inactivating protein, inducing necrosis and apoptosis	[153]
		Bleomycin	Induces double and single stranded DNA break, leading to apoptosis	[149]
		Ricin toxin	Ribosome-inactivating protein, inducing necrosis and apoptosis	[150]
	Suicide genes	Tyrosine kinase (TK)	Converts prodrug to toxic molecules, leading to apoptosis of infected and bystander cells	[138]
		Cytosine deaminase (CD)		[275],[276]
Immune Modulation	Delivery of cancer antigens and immune stimulators	TAAs and neoantigens	Deliver tumor antigens to APCs, initiating a tumor-specific adaptive immune response	[169–173]
		Immunostimulatory cytokines	Enhance APC activation and antigen presentation, increase tumor-specific T cells and B cells	IL-2 [165], IL-12 [277], IL-18 [278], GM-CSF [279]
		TLR activators		CpGDNA [173,174,280], Flagellin [176,177], E8Pam2Cys[175,176]
	Transgene relieving immuno-suppressive TME	GM-CSF	Stimulates proliferation of granulocytes and monocytes, recruitment and maturation of DCs	[161,162]
		sFlt-1	Sequester VEGF, inhibiting angiogenesis	[281]
		Anti-PD-1	Blocks PD-1 mediated inhibition of T cell activation	[173,282]
		Anti-CTLA-4	Blocks CTLA-4 mediated inhibition of T cell activation	[167,168]
Gene Regulation	Gene replacement therapy	p53 transgene	Restore p53 function, inducing cell cycle arrest and apoptosis	[180,188,283]
	Gene modulation	siRNA	Knock down of oncogenic genes, inhibiting growth or inducing apoptosis	[284]
		Non-coding RNA complementary to oncogenic miRNA	Modulates miRNA environment to promote expression of tumor suppressor genes	[195]