Personalized peptide vaccination for advanced colorectal cancer.

We have developed a novel approach in cancer immunotherapy, the personalized peptide vaccination (PPV), in which human leukocyte antigen (HLA)-matched peptides are selected on the basis of preexisting host immunity before vaccination. Recently, we demonstrated the feasibility of PPV in previously treated patients with advanced colorectal cancer, thus warranting further clinical development of this approach.

Phase II study of personalized peptide vaccination for previously treated advanced colorectal cancer.

The prognosis of advanced colorectal cancer (aCRC) remains poor, and development of new therapeutic approaches, including immunotherapy, is needed urgently. Herein we report on our phase II study of personalized peptide vaccination (PPV) in 60 previously treated patients with aCRC, who had failed at least one regimen of standard chemotherapy and/or targeted therapy. For PPV, a maximum of four HLA-matched peptides were individually selected from a pool of 31 different peptide candidates based on preexisting host immunity, and administered subcutaneously without severe adverse events. Boosting of IgG and cytotoxic T lymphocyte (CTL) responses specific to the administered peptides was observed in 49% and 63%, respectively, of the patients, who completed the first cycles of six vaccinations. Median overall survival (OS) time was 498 days, with 1- and 2-year survival rates of 53% and 22%, respectively. Multivariate Cox regression analysis of prevaccination factors showed that plasma IL6, IP-10, and BAFF levels were significantly prognostic for OS [hazard ratio (HR), 1.508, P = 0.043; HR, 1.579, P = 0.024; HR, 0.509, P = 0.002, respectively]. In addition, increased peptide-specific CTL responses after vaccination were significantly predictive of favorable OS (HR, 0.231; P = 0.021), suggesting a causal relationship between biologic and clinical efficacy of PPV. On the basis of the safety profile and potential clinical efficacy, we believe that clinical trials of PPV would be warranted for previously treated patients with aCRC.

Minichromosome maintenance protein 7 is a risk factor for recurrence in patients with Dukes C colorectal cancer.

BACKGROUND: It has been hypothesized that minichromosome maintenance (MCM) proteins, which are replicative control factors, can be used to detect tumor proliferation. The aim of the present study was to investigate the expression of MCM in colorectal cancer tissues and correlate it to clinical outcomes. PATIENTS AND METHODS: The study included 145 patients with colorectal cancer who underwent curative surgery, from January 2002 until December 2004, at the Kurume University Hospital in Fukuoka, Japan. The median follow-up duration was 87 months. The expression of MCM7 in tissues was studied by immuno-histochemical staining. The labeling index (LI) of MCM7 was calculated by dividing the number of positively-stained cells by the total number of cells counted. We divided samples into two groups: positive (MCM7 LI 76% or higher) and negative (MCM7 LI less than 76%). RESULTS: In patients with Dukes A and B, there were no significant differences in either overall survival (OS) or recurrence-free survival (RFS) between patents with MCM7-positive and those with MCM7-negative disease. On the other hand, in patients with Dukes C, there was significantly worse OS and RFS for patients with MCM7-positive compared to those with MCM7-negative disease. CONCLUSION: We found that the expression of MCM7 is an independent risk factor for RFS in patients with Dukes C colorectal cancer. Further studies are required to investigate the validity of MCM7 protein expression for its potential clinical use in colorectal cancer therapy and prognosis.

Virchow lymph node metastatic recurrence of sigmoid colon cancer with severe lymph node metastases successfully treated using systemic chemotherapy combined with radiotherapy.

Metastatic recurrence of colon cancer in the left supraclavicular lymph node (Virchow lymph node) is rare, and to date there are no reports on radiotherapy as treatment. We report on a case of metastatic recurrence of sigmoid colon cancer in the Virchow lymph node with severe lymph node metastases successfully treated with a combined modality therapy of systemic chemotherapy and radiotherapy. The case is of a 58-year-old man, who underwent sigmoid excision and lymph node excision, and subsequently received systemic chemotherapy. After left supraclavicular lymph node recurrence appeared he later received radiotherapy. Complete response was achieved, and there has been no further recurrence, to date, 10 months after the radiotherapy. Radiotherapy was effective as a local treatment, and local control of distant metastasis of colonic cancer may lead to a good prognosis.

[A trial using maximum preoperative chemotherapy for metastatic colorectal cancer].

There are chemotherapy methods applied before operation, before and after operation, or after operation for metastatic colorectal cancer. But the correct times and periods, etc., for their administration have not been obvious. We perform maximum preoperative chemotherapy to control micrometastases, and afterwards surgically remove the metastatic lesions[including radiofrequency ablation(RFA)]. Complications after operation and the severity of pathological liver damage etc., were investigated by comparing 14 patients who received maximum preoperative chemotherapy(group A), with 4 patients for whom 6 courses of FOLFOX+bevacizumab(BV)therapy(group B)were planned. ICG15 before liver resection and bleeding during liver resection were not significantly different(p=0. 26 and p=0. 60, respectively). No severe complication after operation was seen and pathological liver damage was minor in both groups. No interference of maximum preoperative chemotherapy with BV to metastatic colorectal cancer was suggested from the point of view of complications after operation and the severity of pathological liver damage. Further investigation with many more patients is necessary.