Table 5.

List of phages utilized for cancer theragnostic.

Phage	Functional Peptide Display/Cargo	Tumor Type	Mode of Therapy	Preclinical Model	Therapy Outcome	References
M13	WDC-2 phage displaying melanoma cell targeting peptide TRTKLPRLHLQS	Melanoma	Immunomodulatory	Subcutaneous B16-F10 tumor model in mice	Delayed tumor growth and increased survival	[197]
λ Phage	Display of human ASPH-derived proteins	Hepatocellular carcinoma	Immunotherapy—Delivery of antigen for vaccine effect	Prophylactic vaccination schedule in BNL HCC subcutaneous model	Prophylactic and therapeutic immunization significantly delayed HCC growth and progression	[201]
Hybrid M13/AAV	RGD4C peptide CDCRGDCFC that binds to αvβ3 integrin cell surface receptor on Glioblastoma	Glioblastoma	Gene therapy—Grp78 expression	Intracranial implantation of U87 glioblastoma cells	Suppressed the growth of orthotopic glioblastoma	[209]
M13 phage	Fusobacterium nucleatum binding M13 phages	Colorectal cancer	Immunomodulatory	Orthotopic CT26 murine model	Precise scavenging of pro-tumor bacteria of Fusobacterium nucleatum, thereby blocking immunosuppressive myeloid-derived suppressor cells augmentation in the tumor microenvironment.	[28]
2nd generation M13 vector	CDCRGDCFC (RGD4C) ligand that binds to αvβ3 integrin	Chondrosarcoma	Gene therapy–tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) expression	Subcutaneous implantation of SW1353-GFP-Luc cells	Decreased tumor size with nil side effects	[210]
TPA (transmorphic phage/AAV)	Tumour targeting ligand, CDCRGDCFC (RGD4C)	Hepatocellular carcinoma	Therapeutic gene cassette that expresses TRAIL	N/A	Selective and efficient delivery of the tmTRAIL gene to HCC cells that induced apoptotic death of HCC cells	[211]
Transmorphic phage/AAV, TPA	Double-cyclic tumour-targeting ligand, RGD4C ligand	Medulloblastoma	Delivering transgene expressing the tumor necrosis factor-alpha (TNFα)	Subcutaneous Daoy medulloblastoma xenograft mice model	Selective tumor homing, targeted tumor expression of TNFα, apoptosis, and destruction of the tumor vasculature	[212]
M13/AAV	RGD4C ligand on the pIII minor coat protein for targeted therapy Histidine-rich endosomal escape peptide, H5WYG	Chondrosarcoma	Delivery of TNFα transgene	Subcutaneously established SW1353 xenograft in athymic mice	Complete elimination of tumor growth and eradication of the tumor size and tumor viability	[213]
M13 bacteriophage	Chemical cross-linking and biomineralization of palladium nanoparticles	Breast cancer	Delivery of palladium nanoparticle for photothermal therapy and NLG919, a nontoxic IDO1-selective inhibitor	Subcutaneous breast cancer model using 4T1 cells	Induced immunogenic death of tumor cells with down-regulated IDO1 expression	[214]
M13	Fn-binding phages	Colon carcinoma	Immunomodulatory and reversing chemoresistance	Caecum implantation of CT26 cells in BALB/c mice	Modulated gut microbiota to augment chemotherapeutic effect	[215]
M13	Peptide (SYPIPDT) that is able to bind the epidermal growth factor receptor (EGFR) Chemical conjugation of Rose Bengal (RB) photosensitizing molecules on the capsid surface	Epidermoid carcinoma	Photodynamic therapy	N/A	M13EGFR–RB derivatives generated intracellular reactive oxygen species activated by an ultralow intensity white light irradiation, thereby killing the cancer cells	[216]
T7	Cancer homing peptide pep42 (CTVALPGGYVRVC) targeting the grp78 on cancer cells	Melanoma	Mammalian expression cassette of the cytokine granulocyte macrophage-colony stimulating factor (GM-CSF)	Subcutaneous B16F10 xenografts	Inhibited tumor growth by 72% compared to the untreated control.	[217]
M13	Engineered to display the EC and TM domains of human HER2 (ECTM phages) or its splice variant Δ16HER2	Breast carcinoma	Immunotherapy-Delivery of antigen for vaccine effect	Δ16HER2-expressing epithelial tumor cell lines mice	Anti-HER2 vaccination induced a significant anti-HER2 antibody response and controls tumor growth.	[218]
M13	Display of anti-CD40 DARPin into the gene of the pIII coat protein for CD40 targeting	Colon adenocarcinoma	Immunotherapy—In situ vaccines	Subcutaneous MC38 xenografts	Significant accumulation of the phages and activation of DCs at the tumor site, reversing the immunosuppressive tumor microenvironment	[219]
λ Phage	Tumor selectivity of the cargo, apoptin	Breast Carcinoma	Gene therapy	BT-474 cells subcutaneous xenograft	Implanted BT-474 human breast tumor successfully responded to the systemic and local injection of untargeted recombinant λ NBPs	[220]
λ Phage	Display of displaying a HER2/neu derived peptide GP2	Breast carcinoma	Immunotherapy—Delivery of antigen for vaccine effect	Subcutaneous TUBO cell implant	Robust CTL response against HER2/neu-positive tumor challenge in both prophylactic and therapeutic settings	[221]
T4-AAV	RGD peptide (CDCRGDCFC), a cell surface targeting ligand, when fused to the tip of Hoc fiber	HEK293T	Gene delivery, Protein Delivery & Genome editing	N/A	Delivered full-length dystrophin gene and performed genome editing, gene recombination, gene replacement, gene expression, and gene silencing.	[222]
T4	Display of Catalase protein on phage heads Chemically coupled chlorin e6 (Ce6), a photosensitizer	Breast cancer	Photodynamic therapy	Subcutaneous 4T1 cancer cell model	Relieved tumor hypoxia and enabled Ce6 to produce ROS for effective tumor inhibition	[223]
T7 phage	Display of neoepitopes derived from mutated proteins of melanoma tumor cells	Melanoma	Immunotherapy—Delivery of neoepitopes for vaccine effect	Subcutaneous B16F10 xenografts	Rapid production of vaccines that can deliver mutated peptides and stimulate an appropriate B cell response	[224]