Monoclonal antibodies for tumor treatment

A monoclonal antibody, tumor technology, applied in the fields of therapy, antibodies, anti-tumor drugs, etc., can solve the problem of reducing anti-tumor activity and efficacy

Inactive Publication Date: 2011-02-09
CURETECH LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

BAT exerts antitumor activity in athymic nude and beige mice, bu

Method used

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  • Monoclonal antibodies for tumor treatment
  • Monoclonal antibodies for tumor treatment
  • Monoclonal antibodies for tumor treatment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0179] Example 1. In vitro functional assays

[0180] Functional assays are based on the ability of hBAT-1 to increase the survival of cultured murine and human lymphocytes. In this example, the effect of hBAT-1 alone or in combination with chemotherapeutic agents on the enhanced survival of lymphocytes was assessed and expressed by % difference in cell survival or by the area under the dose response curve (AUC expressed as % difference X μg / ml). Chemotherapeutic agents were administered with or 24 hours after hBAT-1 treatment at the indicated concentrations. Chemotherapeutic agents tested by functional assays included 5FU (Figures 1, 2, and 7), SN-38, active derivatives of irinotecan (Figures 3 and 4), cisplatin, oxaliplatin, Taxol (paclitaxel), and dacarba zine (Figures 5 and 7), cytarabine, cyclophosphamide, and doxorubicin (Figure 6).

[0181] The results indicate that specific agents (eg, 5FU, cisplatin, oxaliplatin, paclitaxel, and cytarabine) do not adversely affect...

Embodiment 2

[0182] Example 2. Combination therapy for colorectal cancer

[0183] Colorectal cancer (CT26 tumors) was induced by S.C. injection of CT26 cells, 10 6 Cells / mouse (n=6). The day of injection refers to Day 0. 20 mg / kg of 5-FU was administered I.P. on days 6-9, 15-17, 22-24 and 29-31 , 36-38 and 43-45. On days 10, 18, 25, 32 and 39, 10 mg / mouse of hBAT-1 ( Figure 8-10 ). Relapse cases after complete remission (observed only in the combination therapy group) were further administered with 20 mg / kg of 5FU on days 73-74, 77-80, 85-87, 92-93 and 10 mg / kg I.V. on days 81 and 88. hBAT-1 treatment of mice.

[0184] In a follow-up study of tumor size after one treatment cycle, tumor volumes were measured on alternate days from days 4 to 16 after tumor inoculation. The results showed that combined treatment with 5FU was superior to treatment with 5FU or hBAT-1 alone ( Figure 8 ).

[0185] In a follow-up study of tumor size after 3 alternating treatment cycles, tumor volumes w...

Embodiment 3

[0187] Example 3. Combination Therapy for Melanoma

[0188] with B16 melanoma cells at 5x10 5 Cells / mouse Mice (n=7) were inoculated subcutaneously. The day of inoculation refers to day 0. 50 mg / kg of 5-FU was administered intraperitoneally on days 1-4 and 7-8. In the combined treatment group, a single dose of 10 mg / mouse of hBAT-1 was injected intravenously on the 10th day.

[0189] Monitoring of percent survival began on day 8. The percent survival in mice treated with combination therapy was significantly higher than in mice treated with high doses of 5FU ( Figure 11 ).

[0190] Otherwise stated, combination therapy using a sequential administration schedule in which the humanized antibody was administered after a 9-day cycle of 5FU at dose-limiting toxicity (DLT) levels (50 mg / kg / day) resulted in enhanced survival of mice. The results clearly show that the combination therapy improves tolerance to DLT levels of 5-FU.

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Abstract

The present invention relates to methods for inhibiting tumor growth, increasing survival of a subject having a tumor and inducing protection against tumor recurrence in a mammal. The methods comprise administering a humanized monoclonal antibody comprising CDR regions derived from the murine monoclonal antibody designated mBAT-1, in combination with at least one chemotherapeutic agent.

Description

field of invention [0001] The present invention relates to methods of inhibiting tumor growth, increasing survival of a subject bearing a tumor, and inducing protection against tumor recurrence in a mammal. The method comprises administering a humanized monoclonal antibody comprising CDR regions derived from a murine monoclonal antibody designated mBAT-1 in combination with at least one chemotherapeutic agent. Background of the invention [0002] Knowledge about the molecular and cellular basis of immune regulation, especially at the level of T-cell responses, has grown rapidly in recent years, providing a new arsenal for the development of immunotherapeutic approaches, including tumor vaccines. Certain monoclonal antibodies have been shown to have immunomodulatory activity, including the ability to bind to T cell surface determinants and the ability to induce the proliferation, activation, maturation or differentiation of these cells. [0003] BAT (also known as mBAT-1 or ...

Claims

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Application Information

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IPC IPC(8): C07K16/30A61K39/395
CPCC07K16/3061A61N5/00C07K16/18A61K39/39558A61K31/513A61K31/337A61K31/7068A61K31/282A61P35/00A61P35/02A61P43/00A61K2300/00
Inventor R·罗泰姆-耶胡达G·罗迪诺
Owner CURETECH LTD
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