ALPP-Targeted NSCLC Therapy for Low Surface Expression
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Solution Overview
Problem
Existing antibody-drug conjugate treatments for cancers lacking high expression of ALPP/ALPP2 are limited in efficacy, necessitating more effective methods to target these proteins for enhanced cancer therapy.
Innovation Solution
Administering standard-of-care inhibitors or anti-proliferative agents to increase cell surface expression of ALPP/ALPP2, followed by an antibody-drug conjugate targeting these proteins, particularly in combination with EGFR inhibitors, to enhance therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibody-drug conjugate treatments are used for cancers lacking high expression of ALPP/ALPP2, then treatment is administered, but therapeutic efficacy is limited
Solution Approach 1:
The patent applies preliminary action by administering standard-of-care inhibitors or anti-proliferative agents before antibody-drug conjugate treatment to increase cell surface expression of ALPP/ALPP2 proteins. This preparatory step ensures that the cancer cells have sufficient target protein expression levels to respond effectively to the subsequent antibody-drug conjugate therapy, thereby resolving the limitation of low target expression in certain cancer types.
2Reliability
If standard-of-care inhibitors or anti-proliferative agents are administered to increase ALPP/ALPP2 expression, then cancer cell susceptibility to therapy increases, but treatment regimen complexity increases
Solution Approach 1:
The patent employs universality by utilizing standard-of-care inhibitors or anti-proliferative agents that serve dual functions: their primary therapeutic role in treating cancer and a secondary function of upregulating ALPP/ALPP2 cell surface expression. This multi-functionality allows the same drugs to address both cancer treatment needs and target protein expression requirements, thereby increasing susceptibility to antibody-drug conjugate therapy without adding significant regimen complexity.
3Reliability
If combination therapy with EGFR inhibitors and antibody-drug conjugates is used, then treatment outcomes improve and drug resistance is prevented, but treatment cost and complexity increase
Solution Approach 1:
The patent applies parameter changes by modifying the expression level parameter of ALPP/ALPP2 proteins through administration of standard-of-care inhibitors or anti-proliferative agents. This parameter modification creates optimal conditions for antibody-drug conjugate binding and internalization, thereby enhancing treatment outcomes and preventing drug resistance while managing the complexity of combination therapy through targeted molecular parameter optimization.
Data Source
AI summary
Provided are methods of treating a cancer that co-expresses one or more placental alkaline phosphatase (ALPP) proteins and a cancer target antigen in a patient in need thereof, comprising administering to the patient a treatment regimen wherein the treatment regimen comprises administration of one or more standard-of-care inhibitor or anti-proliferative agents that increase cell surface expression of the one or more ALPP proteins and one or more ALPP protein-targeting agents. Also provided are methods of selecting a patient having a cancer that co-expresses one or more placental alkaline phosphatase (ALPP) proteins and a cancer target antigen, comprising: assaying for baseline cell surface expression levels of the one or more ALPP proteins in a biological sample obtained from the patient; and assaying for co-expression of one or more cancer cell surface oncogenic drivers.