Wilms’ tumor 1 -targeting cancer vaccine: Recent advancements and future perspectives

Figures & data

Table 1. Representative clinical trials of WT1peptide vaccine in cancer patients in the last five years.

Author	Phase	n	Vaccine type	Disease	Clinical outcome	Immune response	Note
Nishida^Citation8	2 (randomized)	91	CTL peptide vaccine +GEM vs GEM	Pancreatic cancer	1-year OS (35.7% vs 20.9%) PFS　extension, (HR, 0.66)		WT1 vaccine combined with GEM prolonged PFS and 1-year OS
Nishida^Citation11	2	25	CTL peptide	Ovarian cancer	Longer PFS:		WT1-specific CTL and IgG level are prognostic makers for WT1 vaccine
					% tetramer-high CTL≧0.25% or WT1-235 IgG ≧0.1 U/ml
Oji^Citation12	2	15	CTL peptide	Thymic epithelial Cancer	No CR and PR,SD: 75%	WT1-specific immune response in majority of patients	WT1 vaccine showed antitumor potential against thymic malignancies.
Tsuboi^Citation15	1	14	CTL+ helper peptide	Malignant glioma	SD: 43%, 1-year OS: 36%, mOS: 24.7 weeks		Promising outcomes for patients with malignant glioma
Oji^Citation16	2	45	CTL+ helper peptide	Rare cancers	SD: 33.3% at 3 months	WT1-235 IgG positivity: 88%	WT1 CTL+helper peptide vaccine induced robust immune responses against WT1in patients with rare cancers.
Manning-Geist^Citation17	1	11	Multivalent peptide (galinpepimut-S) +Nivolumab	Ovarian cancer	1-year PFS: 70%	T cell response to WT1 (91%), WT1-IgG Ab (88%)	Galinpepimut-S plus nivolmab demonstrated safety, immune responses and promising 1-year PFS

Abbreviations: CTL, cytotoxic T cell; GEM, gemcitabine; OS, overall survival; PFS, progression free survival; SD, stable disease; mOS, median OS; mPFS, median PFS; CR, complete response; PR, partial response; HR, hazard ratio.

Table 2. Representative clinical trials of DC vaccine targeting WT1 in various cancers and myeloma in the last five years.

Author	Phase	n	Vaccine type	Disease	Clinical outcome	Immune response	Note
Zhang^Citation25	1/2	10	CTL peptide-pulsed DC	Advanced cancer	7SD, Tumor shrinkage: 43%	Correlation between pre-MDSC and immune response	WT1 peptide-pulsed DC vaccination is a potential treatment in advanced cancer
Ogasawara^Citation27	1/2	11	WT1 CTL+MUC1 peptide-pulsed DC+CTx	Head & neck Cancer	DCR: 45%, mPFS: 6.4 months, mOS: 12.1 months	WT1 response: 5/10 (50%)	DC-based immunotherapy combined with chemotherapy demonstrated safety, immune responses and clinical benefits
Ota^Citation29	1/2	48	WT1 CTL+MUC1 peptide-pulsed DC+CTx	Pancreatic Cancer	mPFS: 8.1 months, mOS: 15.1 months	Increased WT1 response in responders	WT1/MUC-DC vaccination combined with first line chemotherapy demonstrated safety and favorable outcome in advanced pancreatic cancer
Nagai^Citation31	1/2a	10	WT1 CTL+MUC1 peptide-pulsed DC	Pancreatic Cancer after resection	3-year OS:77.8%, 3-year RFS:35.0%	Higher infiltration T cells in tumor site	WT1/MUC1-DC vaccination in adjuvant setting in pancreatic cancer was safe and showed clinical benefits
Chung^Citation40	1	10	WT1, CT7, MAGE-A3 mRNA electroporated DC+lenalidomide	Multiple myeloma after ASCT	Enhanced clinical efficacy	DTH(+), Increased cytokine secretion and CD107a expression	Triple antigen mRNA-electroporated DC vaccination plus lenalidomide maintenance in myeloma demonstrated enhanced immune responses and clinical efficacy

Abbreviations: MUC1, mucin 1; CT7, cancer testis antigen 7; MAGE-A3, melanoma-associated antigen-A3; RFS, relapse free survival; MDSC, myeloid-derived suppressor cell; DTH, delayed-type hypersensitivity; CTx, chemotherapy; DCR, disease control ratio; ASCT, autologous stem cell transplantaion.

Table 3. Representative clinical trials of WT1peptide vaccine in hematological malignancies in the last five years.

Author	Phase	n	Vaccine type	Disease	Clinical outcome	Immune response	Note
Nakata^Citation33	2	20	CTL peptide	AML-CR at high risk	2-year RFS: 25%, 2-year OS: 40%	WT1-specific CTL, higher in responders	WT1 vaccine in AML-CR patients demonstrated favorable outcome
Maslak^Citation34	2	22	Multivalent peptide (galinpepimut-S)	AML in CR	Relapse: 68%, mOS from CR: 16.9 months, mOS from diagnosis: 67.6 months	Immune response≧1 assay: 64%	WT1 multivalent vaccine in AML-CR patients prolonged disease-free and overall survival
Ueda^Citation37	1/2	42	DSP-7888	High risk MDS with AZA failure	DCR: 19%, mOS: 8.6 months		WT1 vaccine in high risk MDS showed acceptable safety and clinical activity
Kiguchi^Citation38	2	134	Helper peptide (OCV-501)	Elderly AML in CR	mDFS: 12.1 months (OVC-501) vs 8.4 months (placebo)	Longer OS in immune responder	WT1 helper peptide vaccine in elderly AML-CR patients showed longer DFS compared to placebo control group
Holmberg-Thyden^Citation47	1	5	Multiple-peptides (WT1, NY-ESO1, MAGEA3, PRAME)	High risk MDS	mean OS from Dx: 18.1 months, mean OS from inclusion: 11.3 months	Immune response (-)	Multi-pipeptide cancer vaccine with AZA in high risk MDS patient failed to show immune responses and clinical benefits

Abbreviations: CR, complete remission; AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; AZA, azacitidine; DCR, disease control rate; DFS, disease free survival; Dx, Dx, diagnosis; ORR, objective response rate; NY-ESO1, New York esophageal squamous cell carcinoma 1; PRAME, preferentially expresssed antigen in melanoma.

Table 4. Selected recent preclinical studies on WT1 vaccine.

Author	Study	Findings	Reference
Nakajima	Identification of helper epitopes	Potent induction and maintenance of WT1-specific CTL	^Citation13
		Efficient rejection of WT1^+ tumor
Nakata	CTL+helper peptide vaccine	Strong infiltration of WT1-specific CD8^+ T at tumor sites	^Citation14
		Accumulation of resident memory T cells at tumor sites
Plantinga	Cord blood derived WT1 mRNA or peptide-DC	Production of cord blood-derived DC using a closed bag system.	^Citation51
		An induction of WT1-specific CTL.
Nakagawa	Oral Bifidobacterium longum-WT1 vaccine	T cell response against multiple WT1 epitopes. Tumor reduction. Increase of CD103^+11b^+11c^+DC in Peyer’s patches. Infiltration of CD4, CD8 in tumor sites. Increased WT1-specific IgG	^Citation52
Xiang	Polystyrene nanopeptide conjugated vaccine	Generate strong immune responses than conventional adjuvants	^Citation53
Shimizu	Ionic liquid transcutaneous delivery system	WT1-specific CTLI induction. Tumor growth inhibition. Increased leukocyte infiltration	^Citation54
Kim	Cytoplasmic transduction peptide fused protein DC vaccine	Up-regulation of MHC and co-stimulatory molecules. Th1 polarization. CTL induction	^Citation55
Pearson	CLEC9-WT1 vaccine	Potent priming effect. Stimulation of CD8^+ T cells	^Citation56

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