SHP1-Inhibited Dendritic Cell Vesicles for Antigen Presentation
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Solution Overview
Problem
Current cancer immunotherapy methods, particularly those involving immune checkpoint therapies, face limitations such as low clinical response rates and patient resistance, due to dysfunctional dendritic cells that fail to effectively present cancer-specific antigens, leading to inadequate immune responses.
Innovation Solution
Administering dendritic cell-derived extracellular vesicles (DC-EVs) that have been treated to inhibit src homologous region 2 domain-containing phosphatase-1 (SHP1) and loaded with tumor or infectious agent antigens, enhancing antigen presentation and immune activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dendritic cells are used to present antigens and stimulate immune responses, then immune activation is enhanced, but the effectiveness is limited by low clinical response rates and patient resistance due to dysfunctional dendritic cells
Solution Approach 1:
The patent applies parameter changes by modifying the functional state of dendritic cells through SHP1 inhibition. By changing the phosphorylation status and signaling parameters of dendritic cells, the invention transforms dysfunctional cells into effective antigen-presenting cells, thereby improving clinical response rates and overcoming the limitation of dendritic cell dysfunction in cancer immunotherapy
Solution Approach 2:
The patent uses SHP1 inhibitors as intermediary substances to mediate between the administered antigens and the dendritic cells. The inhibitor acts as a mediator that enables effective antigen presentation by blocking the negative regulatory pathway, thus enhancing immune activation while overcoming patient resistance to conventional immunotherapy
2Duration of action of stationary object
If immune checkpoint therapies are administered to augment antitumor T-cell responses, then long-lasting protection is achieved in some patients, but therapy resistance develops after initial response
Solution Approach 1:
The patent applies preliminary action by pre-activating dendritic cells with SHP1 inhibition and antigen loading before administering them to patients. This preliminary preparation ensures that the dendritic cells are in an optimal state to initiate and sustain long-lasting immune protection, thereby preventing early therapy resistance and extending the duration of immune response
Solution Approach 2:
The patent employs dynamics by using SHP1 inhibition to dynamically regulate dendritic cell function. The inhibitor enables dendritic cells to adaptively respond to tumor antigens and maintain sustained immune activation, thereby overcoming the static limitation of conventional immunotherapy and preventing resistance development through dynamic immune system modulation
Data Source
AI summary
Methods of activating immune response for treating cancer, infections, or other immune-deficient diseases in patients are provided. Also provided are compositions, formulations, and kits for use in such methods, which comprise dendritic cells (DCs), or extracellular vesicles derived therefrom (DC-EVs), in which src homologous region 2 domain-containing phosphatase-1 (SHIP1) expression and/or activity is inhibited and which have been loaded with disease-specific or disease-associated antigens or peptides. Such SHIP1-modified DC-EVs or DCs, or formulations thereof, may be administered to a patient as monotherapy, and/or as a component of combinational therapies with other therapies in the prevention and treatment of cancer and for boosting antigen-specific immune function in the treatment of other diseases. Also provided are methods of making such SHIP1-modified DC-EVs or DCs and formulations thereof.