Colorectal cancer

Treatment.

Anti-tumor immunotherapy is based on applying the anti-tumor xenogenic polyantigenic vaccine (ÕPV) that has been developed in the Institute of Clinical Immunology (a patent of RF ¹ 2192884). The structural distinctions of the xenogenic tumor-associated antigens from the human homological analogs render these antigens highly immunogenic for human. As a consequence, XPV is highly efficient in inducing anti-tumor reactions in cancer patients (a patent of RF ¹. RF ¹ 2192883).

The inducing course of vaccinotherapy consists of 10 subcutaneous immunizations (five at weekly and five at fortnight intervals) and takes about 3 months. The further vaccination schedule is determined depend upon both a disease stage and a health state of a patient.

The treatment is conducted on an outpatient basis.

Infectious safety.

XPV is prepared from murine tumor cells not containing infectious agents which could potentially be pathogenic for humans.

Side effects

The development of an influenza-like syndrome in the form of a body temperature rise up to 380 C and musculoskeletal discomfort is possible. Those symptoms are usually self- limited. The immunotherapy has no severe side effects attributable to conventional chemoradiotherapy

Clinical effect.

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

XENOVACCINOTHERAPY FOR COLORECTAL CANCER

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 standard cytotoxic therapy including chemotherapy and radiotherapy. On the other hand, evidence is accumulated that immune-based approaches may materially affect course of that disease.

Therapeutic vaccination is a strategy that uses tumor-associated antigens (TAAs) to induce an tumor-specific immune process. Although both autologous and allogeneic cell vaccines are well studied, we favor a xenogenic vaccine. Evidence has been accumulated to demonstrate that the xenogenic TAAs can be much more effective in eliciting antitumor immune responses than their homological analogs. This is due to two the reasons. First, immediately after being entered the human body, xenogenic cell membranes are opsonized with natural antibodies and further –via the FcR-mediated mechanism- phagocytized by professional antigen-presenting cells (macrophage, dendritic cell) which are capable of effectively generating the development of antitumor T-cell responses ( a patent RF ¹219283). Second, the small structural distinctions of the xenogenic TAA from their human analogues render these TAA highly immunogenic and capable of inducing immune-mediated, antitumor responses in a patient not only at early, but also at late, advanced, stages of a disease, when tumor-derived immunosuppression is significant.

The specific immunotherapy is able to generate a selective and long-term antitumor effect. Such therapy incorporates the possibility of a complete recovery from residual disease and has no complications attributable to chemotherapy.

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.

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 metastases.

Two cases of applying xenovaccinotherapy are described in detail 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 ìì 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 .

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Deceases & treatment

• Specific immunotherapy (xenovaccinotherapy) for cancer
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