Colorectal cancer

The inducing course of immunotherapy consists of 10 subcutaneous vaccinations (five at weekly and five at fortnight intervals) and takes about 3 months. The supporting vaccination schedule is determined by both a disease stage and a health state of a patient. The treatment is conducted on an outpatient basis.

The vaccine-induced, immune processes destroy the tumor cells and suppress the development of residual disease.

Xenogenic polyantigenic vaccine (XPV) is sterile.

The development of an influenza-like syndrome in the form of a body temperature rise up to 38°, but also and musculoskeletal discomfort are possible. Those symptoms are usually self-limited. The immunotherapy has no side effects attributable to chemoradiotherapy.

xenovaccinotherapy for colorectal cancer

Therapeutic vaccination is a strategy that uses tumor-associated antigens to induce tumor-specific, immune responses. The xenogenic (murine) polyantigenic vaccine (XPV) -in which there are main families of common tumor associated antigens - has been developed in the Institute of Clinical immunology. The small structural distinctions of xenogenic tumor-associated antigens from their human analogues render these antigens highly immunogenic and capable of stimulating immune-mediated, antitumor responses in a patient not only at early, but also at late stages of a disease, when tumor-derived immunosuppression is significant for more information.

Colorectal carcinoma is one of the most common cancers. Surgical resection of early-stage localized disease is the only curative treatment. Advanced colon cancer is usually resistant to cytotoxic therapy including chemotherapy and radiotherapy. On the other hand, evidence is accumulated that immune-based approaches may materially affect course of that disease.

We evaluated the overall 2-year survival in 37 vacccine-treated, colorectal cancer patients. Their characteristics are presented in Table 1. All patients had measurable or evaluable disease. The control group was composed retrospectively of the patients who received conventional therapy. Each control patient was randomly selected to be a clinically comparable counterpart of a trial patient, so that control and trial groups were evenly balanced by both prognostic and clinical parameters. Throughout follow-up time the trial patients received no any systemic therapy other than immunotherapy.

Table 1. Characteristics of the patients assessable for survival.

Characteristic	Trial	Control
Number of patients	37	37
Males/females	20/17	20/17
Age, years (median, range)	61.1 (38-79)	48.2 (30-80)
Site of metastases:
Lymph node, skin/soft tissue	17 (46%)	17 (46%)
Lung	8 (22%)	6 (16%)
Liver	27 (73%)	19 (51%)
Other organs	11 (30%)	8 (22%)
Prior treatment:
Surgery	19 (51%)	17 (46%)
Surgery + chemotherapy	9 (24%)	8 (22%)
Surgery + radiotherapy	3 (8%)	5 (13%)
Surgery + chemotherapy + radiotherapy	1 (3%)	1 (3%)
Radiotherapy	1 (3%)	1 (3%)
No treatment	4 (11%)	5 (13%)

As shown in Figure 1, the median survival in the XPV-treated patients was significantly longer (P < 0.05) than was the control patients (17 vs 7 months). The overall 2-year survival rate in XPV-treated and control group was 27% (10 patients) and 3% (1 patient), respectively. Clinical effect of various grade (complete response, partial response and disease stabilization) with duration of not shorter than 6 months was observed in 23 (62%) of 37 trial patients.

Figure 1. Survival of the control (n=37) and XPV-treated (n=37) patients.

It is important to note that vaccine-treated in our own study were the patients with very advanced disease. Their majority had initially unresectable metastases. We believe that the xenovaccinotherapy has to be most effective, when it is started as early as before or immediately after surgical resection of primary tumor and its regional metastases.

The examples of applying xenovaccinotherapy for metastatic colorectal cancer are described below.

Case 1. A 51 year-old female patient was admitted to the surgery department with acute bowel obstruction in December 2001. Laparotomy was carried out. Tumor conglomerates were noted in the sigmoid colon, but also in the retroperitoneal space and in the left uterine appendage. Moreover, the abscess of mesocolon was revealed. Cytoreductive surgery with making a colostomy was performed. A mucus-producing adenocarcinoma was diagnosed by histological analysis. The vaccinitherapy was initiated in January 2002. The treatment was well tolerated. The secondary changes (until 25 mm) were detected in the liver in September 2002. Ultrasound investigation (UI) also revealed the tissue mass of size of 34 x 27 мм in the retroperitoneal space on the left. For this reason the vaccinotherapy was continued in the inducing regimen. In June 2003, UI and computerized tomography (CT) both revealed no signs of metastatic lesions in the liver. The reconstructive surgery ( removal of a colostomy and making a colon anastomosis) was performed in Yanuary 2004. In the final analysis, at 3 years following vaccinotherapy initiation the patient was in good condition, had no complains. The tissue mass (45-41mm) kept in the retroperitoneal space.

Case 2. A 46 year-old male patient underwent surgery for reason of colon cancer. A low-grade differentiated adenocarcinoma was diagnosed by histological analysis. The focal lesion of 15 mm was revealed in the liver by UI in Yanuary 2000. For this reason the vaccinotherapy was initiated. No the secondary changes in the liver were detected by UI in June 2001. In the final analysis, at 4 years after vaccinotherapy initiation the patient was in good condition, had no signs of disease.

For more information see the publications.