NK Cell-Mediated PD-L1 Induction for Anti-PDL1 Therapy
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Solution Overview
Problem
Current cancer therapies targeting the PD-L1/PD-1 pathway are limited to patients with PD-L1 positive tumors, as they rely on the initial induction of PD-L1 by the immune system, which is not present in all cancer types.
Innovation Solution
Administering NK cells, such as expanded memory NK cells, in combination with anti-PDL1 antibodies, where the NK cells are activated or expanded using PM21 particles, EX21 exosomes, or FC21 feeder cells, to induce PD-L1 expression on cancer cells and subsequently target them with the antibody.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-PD-L1 therapy is used, then tumor cells with PD-L1 expression can be targeted, but the therapy is limited to patients with PD-L1 positive tumors only
Solution Approach 1:
The patent applies preliminary action by using NK cells to induce PD-L1 expression on tumor cells before administering anti-PD-L1 therapy. This preliminary induction of PD-L1 creates the necessary target for the subsequent antibody therapy, enabling treatment of tumors that would otherwise be PD-L1 negative.
Solution Approach 2:
The patent uses NK cells as an intermediary to bridge the gap between tumor cells and anti-PD-L1 therapy. The NK cells serve as a mediator that induces PD-L1 expression on tumor cells, making them susceptible to antibody-mediated destruction, thus expanding the therapeutic applicability beyond pre-existing PD-L1 positive tumors.
2Reliability
If PD-L1 expression is induced by immune response, then anti-PD-L1 therapy becomes effective, but this relies on a strong initial immune response which is not present in all cancers
Solution Approach 1:
The patent applies self-service by using NK cells that can autonomously induce PD-L1 expression on tumor cells without requiring a pre-existing strong immune response. The NK cells serve their own function of creating the therapeutic target, enabling anti-PD-L1 therapy to work in cancers that would otherwise have weak or absent immune responses.
Solution Approach 2:
The patent uses preliminary action by having NK cells induce PD-L1 expression before anti-PD-L1 therapy is administered. This creates the necessary target independently of the tumor's inherent immune response, enabling treatment of cancers with weak or absent initial immune activity.
3Adaptability or versatility
If NK cells are used to induce PD-L1, then treatment can be given to PD-L1 negative tumors, but the complexity of the treatment protocol increases
Solution Approach 1:
The patent merges the functions of tumor targeting, PD-L1 induction, and immune activation into a single NK cell product. This combination approach, while increasing protocol complexity, enables treatment of PD-L1 negative tumors by integrating multiple functions into one therapeutic agent rather than requiring separate interventions.
Data Source
AI summary
Disclosed are compositions and methods relating to the treatment of a cancer via the induction of PDL1 and use of anti-PDL1 antibodies.