Co-Delivery Therapeutic Constructs for Targeted Cancer Immunotherapy
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Solution Overview
Problem
Current immune checkpoint inhibitors and mitotic kinase inhibitors have limited efficacy and significant toxicity issues, with immune-related adverse effects and dose-limiting side effects, respectively, necessitating targeted delivery to improve cancer treatment outcomes.
Innovation Solution
Development of therapeutic constructs for co-delivery of mitotic kinase inhibitors and immune checkpoint inhibitors using engineered particles or chemical linkers to localize both drugs in cancer cells, enhancing therapeutic index and reducing systemic toxicities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint inhibitors are administered systemically, then immune response is activated, but immune-related adverse effects occur due to uncontrolled systemic immune response
Solution Approach 1:
The patent segments the immune activation process by using different checkpoint inhibitors (anti-PD-L1, anti-PD-1, anti-CTLA-4) that can be selectively combined with specific chemotherapy agents. This segmentation allows controlled immune activation at different levels, reducing uncontrolled systemic immune response while maintaining cancer treatment efficacy.
Solution Approach 2:
Chemotherapy agents serve as intermediaries that first damage cancer cells and release tumor antigens, which then trigger a controlled immune response. This intermediary approach ensures that immune activation is driven by actual tumor presence rather than systemic administration alone, reducing off-target immune-related adverse effects.
2Reliability
If mitotic kinase inhibitors are administered at sufficient doses to achieve tumor bioavailability, then cancer cell killing is enhanced, but dose-limiting toxicity to hematopoietic precursor cells increases
Solution Approach 1:
The patent merges mitotic kinase inhibitors with chemotherapy agents and immune checkpoint inhibitors into combination regimens. This merging allows lower doses of mitotic kinase inhibitors to be used in combination with other mechanisms of action, achieving sufficient tumor bioavailability and cancer cell killing while reducing dose-limiting toxicity to hematopoietic precursor cells.
Solution Approach 2:
The patent employs composite treatment approaches combining multiple therapeutic agents (chemotherapy agents, mitotic kinase inhibitors, immune checkpoint inhibitors) that work through different mechanisms. This composite strategy achieves synergistic anti-tumor effects while distributing toxicity across multiple agents at lower individual doses, reducing hematopoietic precursor cell toxicity.
3Reliability
If combination therapy with chemotherapy and immune checkpoint inhibitors is used, then cancer treatment outcomes are improved, but treatment complexity and potential adverse effects increase
Solution Approach 1:
The patent optimizes combination regimens by adjusting dosing schedules, timing, and specific agent selections based on cancer type and patient characteristics. This parameter optimization maintains improved cancer treatment outcomes while reducing unnecessary treatment complexity through evidence-based regimen selection.
Data Source
AI summary
Disclosed herein are therapeutic constructs including a delivery particle, at least one anti-cancer agent (e.g., a mitotic kinase inhibitor), and at least one immune checkpoint inhibitor. Also disclosed are therapeutic constructs including a mitotic kinase inhibitor, an immune checkpoint inhibitor, and a chemical linker. These therapeutic constructs cause cancer death by both therapeutic and immune effects and promote targeted delivery of more therapeutics to the surviving cancer cells in a positive feed-back loop. They enhance therapeutic index of free drugs and can be used intratumorally or systemically. This strategy can treat broad cancer types and is particular useful for cancer without obvious receptors for cancer-targeted delivery of otherwise toxic therapeutics.