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Ablative immunotherapy

A technology of immune response and immune system, applied in the field of therapeutic methods and compositions for treating tumors and pathogen-infected tissues, capable of solving problems such as inability to perceive threats/dangers of human cancer cells

Inactive Publication Date: 2017-04-26
IMMUNOVATIVE THERAPIES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, decades of disappointing results from clinical trials of various types of immunotherapy in humans have demonstrated the inability of the immune system in humans to perceive the threat / danger of human cancer cells, as well as the immune system in rodent models of the same disease

Method used

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  • Ablative immunotherapy
  • Ablative immunotherapy

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Experimental program
Comparison scheme
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Embodiment 1

[0073] To examine the ability of allogeneic Th1 cells to stimulate systemic antitumor immunity in extensively metastatic disease, the following protocol was tested. Lethal doses of tumor cells (comprising BCL1 leukemia, 4T1 breast cancer, and 3LL lung cancer) were infused intravenously into mice on day 0, and tumor cells were injected intradermally to establish solid tumor masses. On day 7, mice were given 1 x 10 5 dose of allogeneic Th1 cells. On day 14, intratumoral injections: (a) normal saline; (b) normal saline + local cryoablated tumor; (c) 10 3 A dose of allogeneic Th1 cells; or (d) either allogeneic Th1 cells + localized cryoablated tumors to treat mice. Results for animals surviving on day 90 are shown below (n=10):

[0074]

Embodiment 2

[0076] To investigate whether the treatment of patients bearing solid tumors could benefit from the present invention, the above experimental design was repeated in animals that received only intradermal injections of tumor to establish a solid tumor mass. The results were similar to those obtained from those animals with metastatic disease.

[0077]

[0078] The combination of Th1 cells and cryotherapy resulted in a high cure rate. Cryotherapy kills tumors by necrosis, which is considered a more pathological type of cell death than death by apoptosis (the type of death caused by chemotherapy). It is thought that cryotherapy makes tumors more immunogenic and thus the combination of allogeneic Th1 cells with necrotic tumor death establishes a type of tumor vaccine leading to systemic antitumor immunity.

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Abstract

The disclosure herein relates generally to immunotherapy and, more specifically, to the use of immunotherapy for treating tumors and pathogen infected tissues. The immunotherapy relates to first priming patients with allogeneic cells designed to be rejected by a Thl mediated mechanism, then inducing in situ necrosis or apoptosis in a tumor or pathogen infected lesion. Necrosis or apoptosis can be induced by methods such as cryotherapy, irreversible electroporation, chemotherapy, radiation therapy, ultrasound therapy, ethanol chemoablation, microwave thermal ablation, radiofrequency energy or a combination thereof applied against at least a portion of the tumor or pathogen infected tissue. One or more doses of allogeneic cells (e.g., Thl cells) are then delivered within or proximate to the tumor or pathogen-infected tissue in the primed patient. The present invention provides an immunotherapeutic strategy to develop de-novo systemic (adaptive) immunity to a tumor or pathogen.

Description

technical field [0001] The present disclosure relates generally to immunotherapy, and more specifically, to therapeutic methods and compositions for the treatment of tumors and pathogen-infected tissues. Background technique [0002] Harnessing the power of the immune system to treat chronic infectious diseases or cancer is a major goal of immunotherapy. Active immunotherapy is an approach aimed at activating the immune system to specifically recognize and destroy tumor or pathogen-infected cells. For more than 200 years, the approach of active immunotherapy has been used to prevent a large number of infectious diseases, including smallpox, rabies, typhoid fever, cholera, plague, measles, chickenpox, mumps, polio, hepatitis B and pneumonia. Cold and diphtheria toxins. [0003] The concept of active immunotherapy is now being used to develop therapeutic cancer vaccines for the purpose of treating existing tumors or preventing tumor recurrence as well as for the treatment an...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/39A61K39/00A61K35/17A61P35/00A61P31/00
CPCA61K35/17A61K39/0011A61K39/39A61K2039/57A61K2039/55588A61K2039/5158A61K2300/00C12N5/0636A61K35/26A61P31/00A61P31/10A61P31/12A61P35/00Y02A50/30
Inventor 迈克尔·哈尔-诺伊
Owner IMMUNOVATIVE THERAPIES