Colorectal cancer vaccines: Tumor-associated antigens vs neoantigens

Table 1 Clinical vaccination trials focused on colorectal cancer patients

Target type	Target molecule	Vaccination strategy	Therapy	No. of CRC Patients	Clinical response	Ref.
TAA	CEA	Altered peptide loaded on DC		10/12	2 CR, 2 SD, 1 MR, 7 PD	[8]
TAA	CEA	CEA peptides pulsed DC		10	2 SD, 8 PD	[9]
TAA	CEA	CEA peptides pulsed DC		10	7 had CTL increase	[10]
TAA	MAGE	MAGE-A-pulsed DC		21	21 PD	[15]
TAA	MAGE	synthesized helper/killer-hybrid epitope long peptide (H/K-HELP) of MAGE-A4		1	SD	[14]
TAA	MUC1	MUC1-mannan fusion protein	Chemo- therapy	18	2 SD, 16 PD	[17]
TAA	MUC1	100-amino acid synthetic MUC1 peptide with Poly-ICLC		39	20 responders (IgG), 19 non-responders	[18]
TAA	MUC1	irradiated allogeneic colorectal carcinoma cell lines with GM-CSF-producing bystander cell line (K562)		9	4 CR, 5 PD	[19]
TAA	Survivin	survivin-2B peptide		15	1 MR, 3 SD, 11 PD	[21]
TAA	WT1	HLA-A or HLA-DR restricted peptides on DCs	Chemo- therapy	3	3 SD	[22]
TAA	RNF43, TOMM34	peptides,with Montanide ISA 51	Chemo- therapy	21	16 SD	[29]
TAA	RNF43, TOMM34	HLA-A*2402-restricted peptides	Chemo- therapy	22	13 CTL induction	[31]
TAA	RNF43, TOMM34	Peptides with Montanide ISA 51		24	6 SD, 18 PD	[30]
TAA + VEGFR	RNF43, TOMM34, FOXM1, MELK, HJURP, VEGFR-1, VEGFR-2	HLA-A2402- restricted peptides with Montanide ISA 51	Chemo- therapy	30	3 PR, 15 SD, 12 PD	[32]
TAA + VEGFR	RNF43, TOMM34, KOC1, VEGFR-1, VEGFR-2	HLA-A*2402-restricted peptides with Montanide ISA 51		19	1 CR, 6 SD, 12 PD	[33]
PPV TAA	cypB, Ick, SART 1-3, ART4	2-4 HLA-A24-restricted Peptides matching to patient’s pre-vaccination immune response with Montanide ISA 51		10	1 PR, 1 SD, 8 PD	[34]
PPV TAA	SART3, Lck, WHS, HNR, MRP3, PAP, EZH2, CEA, PSCA, UBE, Her2/neu, PSA, CypB	2-4 HLA-A24- or HLA-A2 restricted Peptides matching to patient’s pre-vaccination immune response with Montanide ISA 51	Chemo- therapy	7	1 SD, 6 PD	[35]
PPV TAA	SART2-3, Lck, MRP3, EIF4EBP, WHSC2, CypB, CEA, UBE, Her2/neu,	2-4 HLA-A24- or HLA-A2 restricted Peptides matching to patient’s pre-vaccination immune response with Montanide ISA 51	Chemo- therapy	14	3 MR, 3 SD, 8 PD	[36]
Neoantigen	AIM2(-1), HT001(-1), TAF1B(-1)	Frameshift peptides with Montanide ISA 51		22	16 immune response (CTL/IgG induction)	[52]
Neoantigen	KRAS	13-mer ras peptide with Detox adjuvant		10	1 SD, 2 cytotoxic activity	[62]
Neoantigen	KRAS	13-mer ras peptide with Detox adjuvant		7	4 remained with no evidence of disease	[64]
Neoantigen	KRAS	13-mer ras peptide with Il-2 or GM-CSF or both		38	4 SD, 34 PD	[66]

CRC: Colorectal cancer; CR: Complete response; CTL: Cytotoxic T lymphocyte; DC: Dendritic cell; GM-CSF: Granulocyte macrophage colony-stimulating factor; HLA: Human leukocyte antigen; MR: Minor response; PD: Progressive disease; PR: Partial response; SD: Stable disease; CEA: Carcinoembryonic antigen; TAA: Tumor-associated antigen.