Kidney 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 KIDNEY CANCER

Although curative treatments for kidney cancer involve removing the local (primary) tumor, cancer that has spread beyond the kidney requires treatment of all areas of the body (systemic therapy). Consequently, a lot of attention is now focused on a relatively new approach to treatment of kidney cancer called immunotherapy. The goal of immunotherapy is to boost the body's immune system to more effectively fight off or destroy cancer cells. There are several types of immunotherapy used to treat patients with metastatic renal cancer. Use of cytokines (proteins that activate the immune system) has become one of the standard treatments for metastatic disease. The two cytokines most often used are interleukin-2 (IL-2) and interferon-alpha. Both cytokines can cause partial or complete response in about 20% patients. In addition, many patients cannot tolerate the side effects of such therapy.

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 high-dose cytokine immunotherapy.

According the available data (Davydov et al. 2006 ), the median survival in patients with disseminated renal cancer is typically on the order of 6–to-12 months, and the overall 2 year survival rate is nearly 10% . The data on 3-year survival of 13 xenovaccine-treated patients (8 male, 5 female; age from 54-to-70) with IV stage renal cancer is shown in Figure 1.

Survival

Figure 1. Survival of the XPV-treated kidney cancer patients (n=13)

The presented data are very encouraging. Nevertheless, they must be considered as preliminary because they are based on a very small number of patients.

Two examples of applying xenovaccinotherapy are described in detail below.

A 64-old female patient T (a history ¹ 2057) diagnosed with clear cell cancer of the right kidney (T4NxMx) (the condition after a surgical inspection of the abdominal cavity) started to vaccinate in October 2002. At that time there were complains of marked pains in the region of abdomen on the right. The elevated ESR (40 mm/h) was noted in the blood analysis. The excretory kidney function was not disturbed. As revealed by computer tomography (CT), a tumor (76 õ 60 õ 100 ìì) of the right kidney was intimately adjacent to the liver. The vaccinotherapy was well tolerated. After vaccination the induration of 30-to-40 mm usually developed in the injection site. At 3 months after vaccinotherapy initiation ERS reduced to norma (11 mm/h). UI revealed no sighs tumor growth. In the final analysis, at 2.5 years after vaccinotherapy initiation there was no evidence for disease progression.

A 61-old female patient Ò (a history ¹ 1003) firstly underwent a surgery for reason of developing cysts in the left kidney in November 1990. One month later this kidney was ablated. Metastases of clear cell hypernephroma cancer were detected in the right ovary in February 1993. The uterus with its appendages was surgically ablated and, after which, a course of immunotherapy with interferon was conducted. The sights of multifocal tumor lesions of the right kidney and adrenal gland were revealed by CT in November 2001. For this reason vaccinotherapy was initiated. In the final analysis, at 3 years after vaccinotherapy initiation the state of the patient was stable, there was no evidence for disease progression.

A 64-old female patient T (a history ¹ 2057) diagnosed with clear cell cancer of the right kidney (T4NxMx) (the condition after a surgical inspection of the abdominal cavity) started to vaccinate in October 2002. At that time there were complains of marked pains in the region of abdomen on the right. The elevated ESR (40 mm/h) was noted in the blood analysis. The excretory kidney function was not disturbed. As revealed by computer tomography (CT), a tumor (76 õ 60 õ 100 ìì) of the right kidney was intimately adjacent to the liver. The treatment was well tolerated. After vaccination the induration of 30-to-40 mm usually developed in the injection site. At 3 months after vaccinotherapy initiation ERS reduced to norma (11 mm/h). UI revealed no sighs tumor growth. In the final analysis, at 2.5 years after vaccinotherapy initiation there was no evidence for disease progression.

A 61-old female patient Ò (a history ¹ 1003) firstly underwent a surgery for reason of developing cysts in the left kidney in November 1990. One month later this kidney was ablated. Metastases of a clear cell hypernephroma cancer were detected in the right ovary in February 1993. The uterus with its appendages was surgically ablated and, after which, a course of immunotherapy with reaferon was conducted. The sights of multifocal tumor lesions of the right kidney and adrenal gland were revealed by CT in November 2001. For this reason vaccinotherapy was initiated. In the final analysis, at 3 years after vaccinotherapy initiation the state of the patient was stable, there was no evidence for disease progression.

For more information see the publications.

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