Ignite Creation Date:
2024-05-06 @ 7:46 PM
Last Modification Date:
2024-10-26 @ 3:13 PM
Study NCT ID:
NCT06131775
Status:
RECRUITING
Last Update Posted:
2024-06-06
First Post:
2023-10-13
Brief Title:
Characterisation of TLR4 Blood Cells in Patients With Solid Cancer
Sponsor:
Hospices Civils de Lyon
Organization:
Hospices Civils de Lyon
Study Overview
Official Title:
Characterisation of TLR4 Blood Cells in Patients With Solid Cancer
Status:
RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ODYSSEE
Brief Summary:
The potential of immunotherapy in the treatment of cancer is now well documented While excessive activation of the immune system may be associated with severe reactions andor auto-immune syndromes it is now clearly established that controlled activation of the adaptive immune system constitutes a major contribution to the treatment of cancer Antigen-independent activation of the adaptative immune system with immune checkpoint inhibitors ICI has allowed prolonged survival in a minority of patients with previously intractable disease However a variety of tumor indications are still presently inaccessible to immunotherapeutic approaches or poorly responsive to these therapies
The immune system is a highly reactive complex comprising antigen-specific cells adaptive immune system and antigen-agnostic cells innate immune system which interact closely in a complex network The adaptive immune response is mediated by B and T cells upon antigen-specific recognition The innate response is mediated by macrophages dendritic cells Natural Killer cells and assume the immediate defense of the organism against infectious agents The innate immune system plays a key role in antigen processing and presentation production of key cytokines and as anti-tumor effector cells The role of the innate immune system in the control of cancer progression and in cancer therapy is well documented Natural Killer cells involved in antibody-dependent cellular cytotoxicity and cells performing phagocytosis such as macrophages and neutrophils participate in tumor destruction after intervention of adaptive immune cells and in combination with certain tumor-targeting therapies such as antibodies recognizing tumor-specific antigens
The Odyssey project aims to harness the next generation paradigm of cancer immunotherapy systemic stimulation of the innate immune system
To achieve this endeavour the investigator will exploit a well-known yet poorly documented phenomenon ie the rare occurrence of cure in cancer patients who have presented a simultaneous severe septic episode at the time of diagnosis
Several clinical studies have been realized in order to demonstrate the effect of the innate immune response activation by the bacterial LPS lipopolysaccharides in cancer therapy However severe toxicities have been described even at very low dose of LPS The LPS-activated immune response is mediated by TLR4 Toll Like Receptor 4 a transmembrane receptor expressed by several cell types including monocytes and macrophages The interaction of TLR4 with LPS mainly induces the release of proinflammatory cytokines so called canonical pathway TLR4-signalling cascade can also induce the release of type I interferon so called alternative pathway a class of cytokines known to promote antitumoral activity LPS tolerance is presumed to be rather associated with the activation of the alternative pathway Therefore managing this LPS tolerance is a key mechanism that could limit the systemic toxicity of LPS while stimulating the innate immune system
Héphaïstos-Pharma biotech and the CRCL Onco-Pharmacology lab Centre de Recherche en Cancérologie de Lyon have set up a modified formulation of the LPS that improves its pharmacokinetic properties reduces its toxicity and preferentially activates TLR4-alternative signalling pathway Before investigating the effect of this new immunostimulant in a future phase III clinical trial a translational study is required to further characterize the TLR4 positive cells population as well as the innate immune system in patients with solid cancer
The immune system is a highly reactive complex comprising antigen-specific cells adaptive immune system and antigen-agnostic cells innate immune system which interact closely in a complex network The adaptive immune response is mediated by B and T cells upon antigen-specific recognition The innate response is mediated by macrophages dendritic cells Natural Killer cells and assume the immediate defense of the organism against infectious agents The innate immune system plays a key role in antigen processing and presentation production of key cytokines and as anti-tumor effector cells The role of the innate immune system in the control of cancer progression and in cancer therapy is well documented Natural Killer cells involved in antibody-dependent cellular cytotoxicity and cells performing phagocytosis such as macrophages and neutrophils participate in tumor destruction after intervention of adaptive immune cells and in combination with certain tumor-targeting therapies such as antibodies recognizing tumor-specific antigens
The Odyssey project aims to harness the next generation paradigm of cancer immunotherapy systemic stimulation of the innate immune system
To achieve this endeavour the investigator will exploit a well-known yet poorly documented phenomenon ie the rare occurrence of cure in cancer patients who have presented a simultaneous severe septic episode at the time of diagnosis
Several clinical studies have been realized in order to demonstrate the effect of the innate immune response activation by the bacterial LPS lipopolysaccharides in cancer therapy However severe toxicities have been described even at very low dose of LPS The LPS-activated immune response is mediated by TLR4 Toll Like Receptor 4 a transmembrane receptor expressed by several cell types including monocytes and macrophages The interaction of TLR4 with LPS mainly induces the release of proinflammatory cytokines so called canonical pathway TLR4-signalling cascade can also induce the release of type I interferon so called alternative pathway a class of cytokines known to promote antitumoral activity LPS tolerance is presumed to be rather associated with the activation of the alternative pathway Therefore managing this LPS tolerance is a key mechanism that could limit the systemic toxicity of LPS while stimulating the innate immune system
Héphaïstos-Pharma biotech and the CRCL Onco-Pharmacology lab Centre de Recherche en Cancérologie de Lyon have set up a modified formulation of the LPS that improves its pharmacokinetic properties reduces its toxicity and preferentially activates TLR4-alternative signalling pathway Before investigating the effect of this new immunostimulant in a future phase III clinical trial a translational study is required to further characterize the TLR4 positive cells population as well as the innate immune system in patients with solid cancer
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2023-A01542-43 | OTHER | ID-RCB | None |