Immunotherapy for colorectal cancer

Table 1 Immunotherapy strategies for colorectal cancer

Vaccine	Clinical response	Immunological response	Ref.
Peptide
Survivin-2B	PR (1/15)SD (3/15) PD (11/15)Temporary decrease of CEA level 40% (6/15)	Increase of Survivin-2B-specific CTL frequency DTH 40% (6/15)	[48]
Combination chemotherapy with peptide vaccine against RNF43 and TOMM34	SD (16/19)PD (3/19)	8 of 21 patients exhibited antigen-specific CTL responses to both RNF43 and TOMM34, and 12 patients exhibited CTL responses to one of the peptides only	[52]
13-mer mutant ras	Of nine patients who completed all six vaccinations, seven patients showed no remaining evidence of disease	Two CRC patients showed immunological responses, and the antitumor immune response was significantly associated with prolonged overall survival	[53]
β-hCG	Prolongation of survival in patients with a high level of antipeptide antibodies	Induction of serum antipeptide antibody (56/77)	[46]
SART3	Diagnosis at 5 mo after first vaccination:SD (1/19) PD (10/19)	Increased CTL activity (2/11), induction of serum antipeptide IgG (2/12), IgE (5/12), DTH (0/12)	[45]
A set of 10 overlapping p53 synthetic long peptides		Induction of p53-specific CD4+ and CD8+ T-cell responses (9/10), maintained p53-specific CTL reactivity for at least 6 mo (6/9)	[50]
DC
DC pulsed with CEA peptide or CEA mRNA	Disease stabilization was observed in several patients	The majority of CRC patients demonstrated induction of CEA-specific T cell responses	[60-65]
DCs pulsed with CEA-derived altered peptides combined with the adjuvant Flt3 ligand	2 of 12 patients exhibited SD for 3 and 6 mo; 2 patients exhibited CR for more than 10 mo; 1 patient had a mixed response with some regression of liver metastases	Expansion of CD8+ T cells that recognize both the native and altered epitopes and possess an effector CTL phenotype	[64]
Whole tumor cell
Autologous tumor cells combined with BCG	No significant clinical benefit was seen with whole tumor cell vaccines in surgically resected patients with stage II or III CRC	When treatment compliance was evaluated, the trend indicated benefits from vaccination in terms of disease-free survival (P = 0.078) and overall survival (P = 0.12)	[68]
NDV-infected irradiated autologous tumor cells	A randomized phase III study of 50 patients with resectable CRC liver metastases demonstrated that vaccination with NDV-infected whole tumor cell did not significantly improve overall survival.	DTH (21/31)	[74,75]
Viral vector
Replication-defective recombinant fowlpox and vaccinia viruses encoding the CEA antigen and TRICOM (B7.1, ICAM-1, and LFA-3)	SD (3/9)	Induction of CEA-specific CTL (3/9)	[79]
Combination chemotherapy and vaccination with a nonreplicating canarypox virus (ALVAC) expressing the CEA and T-cell costimulatory molecule B7.1 (ALVAC-CEA/B7.1)	Objective response(42/118)	Increases in CEA-specific T cells were detected in patients treated with chemotherapy and booster vaccination	[80]

Immunotherapy strategies including peptides derived from tumor-associated antigens, whole tumor cells, in vitro-generated dendritic cells (DCs), or viral vector-based cancer vaccine. PD: Programmed cell death protein; CTL: Cytotoxic T lymphocytes; CEA: Carcinoembryonic antigen; CRC: Colorectal cancer; RNF43: Ring finger protein 43; TOMM34: Translocase of outer mitochondrial membrane 34; β-hCG: β-human chorionic gonadotropin; SART3: Squamous cell carcinoma antigen recognized by T cells 3; NDV: Newcastle disease virus.