Allogeneic Cell Priming for Tumor Ablation Immunotherapy
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Solution Overview
Problem
Current immunotherapy methods for treating tumors and viral infections are ineffective in overcoming tumor and viral immunoavoidance mechanisms, failing to induce a strong immune response in humans that can eradicate cancer cells and pathogen-infected cells throughout the body.
Innovation Solution
A method involving allogeneic cell therapy, where allogeneic cells are administered to induce anti-allogeneic Th1 immunity, followed by in situ ablation of tumor or pathogen-infected tissue to release antigens, which are then taken up by dendritic cells, matured, and presented systemically to stimulate a strong adaptive immune response, overcoming immune avoidance mechanisms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional active immunotherapy is used to activate the immune system against tumors, then immune cells are generated that can specifically kill tumor cells, but tumor escape mechanisms overpower the immune response resulting in tumor progression
Solution Approach 1:
The patent applies preliminary action by first administering allogeneic cells to prime the immune system before tumor challenge. This pre-activation of immune cells with non-self antigens creates a primed state that enhances subsequent anti-tumor immunity, allowing the immune system to respond more effectively before tumors can establish escape mechanisms
Solution Approach 2:
The patent uses allogeneic cells as an intermediary to bridge and enhance the immune response. These non-self cells act as a mediator that stimulates stronger immune activation and cytokine production, which in turn enhances the effectiveness of endogenous anti-tumor immune cells without directly attacking the tumor
2Reliability
If immunotherapy is applied to treat chronic viral infections, then the immune system can neutralize virus particles and destroy infected cells, but viruses have developed countermeasures to avoid immune attack
Solution Approach 1:
The patent applies preliminary action by pre-priming the immune system with allogeneic cells before viral challenge. This creates a more robust and activated immune state that can better recognize and respond to viral antigens, overcoming viral adaptation strategies that evade conventional immune responses
3Reliability
If allogeneic cells are administered to induce anti-allogeneic Th1 immunity, then a strong adaptive immune response is generated, but the process requires multiple steps including ablation and timing coordination
Solution Approach 1:
The patent uses preliminary action by administering allogeneic cells in advance to establish immune memory and Th1 polarization before tumor ablation. This sequencing ensures that when the tumor is destroyed and antigens are released, the immune system is already primed and activated, reducing the need for additional adjuvants or repeated treatments
Solution Approach 2:
The patent employs periodic action through the structured timing of treatments: initial allogeneic cell administration, waiting period for immune memory formation (7-14 days), ablation procedure, and subsequent allogeneic cell re-administration. This periodic protocol allows immune system recovery and memory formation between stimulation events, enhancing overall effectiveness while managing complexity
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach effectively generates a systemic adaptive immune response capable of eradicating tumors or pathogen-infected cells, overcoming the limitations of existing immunotherapy by creating a robust and specific immune reaction against tumor or pathogen antigens.
Implementation Method 1
administering to a subject with cancer or an infectious disease an aliquot of allogeneic cells that are designed to be rejected by the subject immune system in a manner that induces anti-allogeneic Th1 immunity
Implementation Method 2
performing an in situ ablation of an accessible tumor lesion or pathogen-infected tissue with an ablation method which causes at least a portion of the tumor or infected tissue to die, preferably by necrosis
Implementation Method 3
injecting a second aliquot of the same allogeneic cells intralesionally (same cells as used to prime), preferably 2-24 hrs after the ablation step, creating an immune response that serves as an adjuvant to the uptake of antigen(s) and the subsequent maturation of host antigen presenting cells (i.e., dendritic cells) responding to the necrotic or apoptotic tissue
Data Source
AI summary
The disclosure herein relates generally to immunotherapy and, more specifically, to the use of immunotherapy for treating tumors and pathogen infected tissues. The immunotherapy relates to first priming patients with allogeneic cells designed to be rejected by a Th1 mediated mechanism, then inducing in situ necrosis or apoptosis in a tumor or pathogen infected lesion. Necrosis or apoptosis can be induced by methods such as cryotherapy, irreversible electroporation, chemotherapy, radiation therapy, ultrasound therapy, ethanol chemoablation, microwave thermal ablation, radiofrequency energy or a combination thereof applied against at least a portion of the tumor or pathogen infected tissue. One or more doses of allogeneic cells (e.g., Th1 cells) are then delivered within or proximate to the tumor or pathogen-infected tissue in the primed patient. The present invention provides an immunotherapeutic strategy to develop de-novo systemic (adaptive) immunity to a tumor or pathogen.