Hydroxyprogesterone Caproate Combination Therapy for TIL Infiltration
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Solution Overview
Problem
Conventional tumor treatments, including immunotherapy with PD-1 antibodies, face challenges due to the heterogeneous tumor microenvironment, which impedes drug delivery and immune cell penetration, leading to limited clinical efficacy and resistance mechanisms.
Innovation Solution
A pharmaceutical composition combining hydroxyprogesterone caproate with immune checkpoint inhibitors, such as PD-L1 antibodies, enhances tumor-infiltrating lymphocyte (TIL) infiltration and anti-tumor activity, particularly through formulations like injectable liquids.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If PD-1 antibodies are used for immunotherapy, then immune system activation is improved, but clinical efficacy is limited due to tumor microenvironment heterogeneity
Solution Approach 1:
The patent applies local quality by modifying the tumor microenvironment specifically at the tumor site rather than systemically. Hydroxyprogesterone caproate is administered to create local changes in the tumor microenvironment, including modulation of immune cell infiltration and cytokine production, while maintaining different conditions in various regions of the heterogeneous tumor to overcome resistance mechanisms.
Solution Approach 2:
The patent uses composite materials by combining hydroxyprogesterone caproate with PD-1 antibodies in a combination therapy regimen. This composite approach integrates two different therapeutic mechanisms: the immunomodulatory effects of hydroxyprogesterone caproate and the immune checkpoint inhibition of PD-1 antibodies, creating a synergistic effect that overcomes the limitations of monotherapy.
2Reliability
If conventional chemotherapy and radiation therapy are used, then tumor control is achieved, but toxicity and poor tolerability increase
Solution Approach 1:
The patent uses hydroxyprogesterone caproate as an intermediary substance that mediates between the immune system and tumor cells. Rather than directly attacking tumor cells like conventional chemotherapy, it acts as a mediator to modulate the immune microenvironment, enhance immune cell function, and facilitate immune-mediated tumor destruction, thereby reducing direct toxicity to healthy tissues.
Solution Approach 2:
The patent replaces the mechanical direct-killing mechanism of conventional chemotherapy and radiation with a biological immune-mediated mechanism. Instead of using cytotoxic drugs or ionizing radiation to directly destroy tumor cells, the treatment harnesses the body's immune system to recognize and eliminate tumor cells, substituting a more selective and less toxic mechanism.
3Reliability
If tumor immunotherapy is implemented, then anti-tumor immune response is activated, but immunosuppressive microenvironment hinders effectiveness
Solution Approach 1:
The patent converts the harmful immunosuppressive microenvironment into a beneficial immunostimulatory environment. Hydroxyprogesterone caproate transforms the suppressive conditions created by tumor cells into favorable conditions for immune activation by modulating immune cell differentiation, reducing suppressive cytokine production, and enhancing the functionality of anti-tumor immune cells.
Data Source
AI summary
Provided in the present invention is a pharmaceutical composition comprising hydroxyprogesterone caproate and an additional therapeutic agent for treating tumors, wherein the additional therapeutic agent is preferably a monoclonal antibody against PD-1 or PD-L1. Further provided in the present invention are a method for increasing the number of tumor infiltrating lymphocytes (TIL) as required and a method for treating cancers in a subject in need thereof, which comprises providing the hydroxyprogesterone caproate to the subject.