Gastric 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 GASTRIC CANCER

Gastric cancer is one of the most common cancers. Surgical resection of early-stage localized disease is the only curative treatment. Advanced gastric 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 this disease.

Therapeutic vaccination is a strategy that uses tumor-associated antigens (TAAs) to induce an tumor-specific immune process. The xenogenic (murine) polyantigenic vaccine (XPV) -in which there are main families of common tumor associated antigens (TAA)- has been developed in the Institute of Clinical immunology (a patent RF ¹ 2192884). Xenovaccinotherapy has significant advantages over the vaccinal approaches based on applying homologous (autological or allogeneic) tumor cells or their antigenic derivates. 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 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 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.

Our own experience suggests that a clinical effect of various grades (complete or partial response, disease stabilization) with a duration not shorter than 6 months may be achieved in nearly 55 % stage IV patients. These results should be considered as preliminary because they are based on a very small number of patients with very advanced disease. We suggest that the xenovaccinotherapy might be much more effective, when it is started as early as before or immediately after surgical resection of primary tumor and its metastases.

Two examples of applying xenovaccinotherapy in patients with advanced disease are described in detail below.

A 44 year-old female patient I (a history ¹ 3086) was diagnosed with signet ring cell gastric carcinoma in November 2002.Combined gastrectomy was carried out in December 2002. One course of polychemotherapy was further conducted. In February 2003 signs of disease progression were noted: UI revealed enlarged lymph nodes within both the gate of the liver and the retroperitoneal space. Vaccinotherapy was started in an intensified regime. The treatment was well tolerated. At 3 months after vaccinotherapy initiation UI revealed no signs of disease. The reduction of ESR to norma and the elevation of Hb level were noted in blood analysis In the final analysis, at 2 years after vaccinotherapy initiation the patient was in good condition, no evidence for disease was observed.

A 54 year-old male patient I (a history ¹ 2009) diagnosed with low-grade differentiated, gastric adenocarcinoma, multiple lesions in the left lung (the condition after radiochemotherapy) started to vaccinate in August 2002. At that time there were complains of general weakness, periodic vomiting, and low grade fever. In December 2002 the state of his health became worse. Daily vomiting, lack of appetite, significant loss of weight and intense paints within the epigastric region were noted. In spite of everything, vaccinotherapy was not stopped. In February 2002 the state of the patients was somewhat improved : attacks of vomiting became less frequent, blood parameters returned to norma. UI revealed a lesion of 15 mm diameter in the bottom pole of the right kidney. The patient’s state was stable until June 2002, when gastric obstruction developed. In July 2003 surgery (Bilrot 2 operation) was performed. On surgical inspection no metastases were noted. No pathological signs were detected by UI. A chest x-ray also revealed no tumor signs in lungs. In the final analysis, at 2 years after vaccinotherapy initiation no evidence for disease progression was observed.

For more information see the publications .

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