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Use of local immune suppression to enhance oncolytic viral therapy

An oncolytic virus and immunosuppression technology, applied in the field of local immunosuppression, can solve the problem that the treatment effectiveness is not optimal.

Inactive Publication Date: 2009-03-04
ONCOLYTICS BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the effectiveness of oncolytic virus therapy has largely been demonstrated in preclinical studies, the effectiveness of therapy in clinical trials is still suboptimal.

Method used

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  • Use of local immune suppression to enhance oncolytic viral therapy
  • Use of local immune suppression to enhance oncolytic viral therapy
  • Use of local immune suppression to enhance oncolytic viral therapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0087] Example 1. In vitro and in vivo radiation increases reovirus cytotoxicity

[0088] The Ras signaling pathway determines the radiosensitivity of tumor cells. Ras activation promotes tumor cell survival after exposure to radiation. Ras activation is associated with increased radiation resistance in vitro and in vivo. To determine whether reoviruses enhance reovirus cytotoxicity in vitro, cells were plated and either treated with 5 Gy or sham. After 4 hours, serotype 3 reovirus (Dearing strain) was administered to the cells. Cell viability was quantified using crystal violet. figure 1 It was shown that radiation of only 5 Gy enhanced reovirus cytotoxicity.

[0089] To determine radiation and reovirus effects in vivo, fractionated radiation therapy and reovirus (intrathecal administration) were administered to mice with HCT116 xenograft tumors ( Figure 2A ) or B16 syngeneic tumors ( Figure 2B )middle. Figure 2 shows that administration of radiation and reovirus is...

Embodiment 2

[0091] Example 2. Effects of Reovirus and Radiation Therapy on Humans

[0092] The study design to determine the effects of reovirus and radiotherapy in humans is shown in Table 1.

[0093] Table 1. Study Design

[0094] stage patient x group Dosage of Reolysin

(TCID50) RT(Gy) viral

dose Virus

Dosing day Ia 3 1 x 10 8 20Gy, 5F 2 2，4 Ia 3 1 x 10 9 20Gy, 5F 2 2，4

[0095] Patients were included on the basis of measurable disease (target lesion), indicated palliative RT, PS (ECOG) ≤ 2, adequate hematology, renal and hepatic function. Patients with irradiated lesions or patients receiving immunosuppressive therapy or known HIV, Hep B or C infection were excluded.

[0096] The amount of Reolysin depends on the target volume of the lesion. Tumor volumes were calculated from measurements of three orthogonal diameters (D1, D2 and D3) and using the equation V=π / 6 x D1 x D2 x D3. Tumors received injection volumes ranging fr...

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Abstract

Provided herein are methods for treating or ameliorating a solid tumor in a subject comprising administering oncolytic viruses and immunosuppressive agents at or near the site of the tumor.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Serial No. 60 / 773,068, filed February 13, 2006, and U.S. Serial No. 60 / 788,898, filed April 3, 2006, both of which The entire content of this application is incorporated herein by reference. technical field [0003] The present invention relates to the use of local immunosuppression in subjects receiving oncolytic virus therapy to improve therapeutic efficacy. Background technique [0004] In the United States alone, more than one million people are diagnosed with cancer each year. Despite advances in medical research, cancer remains the second leading cause of death in the United States. In developed countries, about one in five people die from cancer. In the search for new strategies, oncolytic virus therapy has recently emerged as a viable approach to specifically kill tumor cells. Unlike traditional gene therapy, it uses replicable viruses capable of spreading through t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/76A61N5/00A61P35/00
Inventor M·C·科菲B·G·汤普逊
Owner ONCOLYTICS BIOTECH
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