HERV-E Antigen Targeted CD8+ T Cell Therapy for Renal Cell Carcinoma
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Solution Overview
Problem
Current treatments for renal cell carcinoma (RCC) are often ineffective and have adverse effects, with a lack of specific and less toxic alternatives, and there is a need for better understanding of immune cells and their target antigens to develop more effective transplant approaches.
Innovation Solution
A composition comprising an isolated enriched CD8+ T cell or dendritic cell population reactive to a human endogenous retrovirus type E antigen, which includes an envelope protein or polymerase protein, is used to treat or prevent neoplastic diseases, specifically targeting metastatic solid tumors like RCC, by administering an allogeneic or autologous cell population or the antigen itself to reduce or eliminate tumors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for renal cell carcinoma are used, then tumor reduction may be achieved, but adverse effects and toxicity increase
Solution Approach 1:
The patent uses human endogenous retrovirus type E (HERV-E) antigens as intermediaries to activate the patient's own immune system against tumor cells. Instead of directly administering toxic chemotherapy agents, the invention employs viral antigens that serve as mediators to stimulate endogenous CD8+ T cells to recognize and destroy tumor cells expressing HERV-E antigens, thereby reducing toxicity while maintaining anti-tumor effectiveness
Solution Approach 2:
The invention enables the patient's immune system to serve itself by activating endogenous CD8+ T cells through HERV-E antigen stimulation. The patient's own immune cells are harnessed to recognize and eliminate tumor cells, eliminating the need for external toxic substances and allowing the body's natural defense mechanisms to combat the cancer
2Reliability
If allogeneic T-cell transplantation is performed, then graft-versus-tumor effect is enhanced, but graft-versus-host disease occurs
Solution Approach 1:
The patent extracts and utilizes only the anti-tumor beneficial effects of allogeneic T-cell transplantation by specifically targeting HERV-E antigens expressed on tumor cells. By focusing the immune response on tumor-specific antigens rather than general alloreactivity, the invention separates the desired graft-versus-tumor effect from the harmful graft-versus-host effect, achieving selective tumor destruction without widespread tissue damage
Solution Approach 2:
The invention applies local quality by directing the immune response specifically to tumor cells expressing HERV-E antigens rather than affecting all tissues uniformly. The allogeneic T cells are stimulated to recognize and attack only the tumor cells with the specific viral antigen marker, leaving healthy host tissues spared from immune attack
3Duration of action of stationary object
If immunosuppression is maintained to prevent rejection, then graft survival is improved, but tumor regression is delayed
Solution Approach 1:
The patent changes the immunological parameters by introducing HERV-E antigens that create a new recognition target for T cells. This antigen-specific stimulation allows the immune system to distinguish between tumor cells and healthy tissues, enabling effective anti-tumor responses without requiring strong immunosuppression that would delay tumor regression. The parameter change from general self-tolerance to antigen-specific recognition resolves the timing conflict
Data Source
AI summary
Compositions and methods are provided for preventing or treating neoplastic disease in a mammalian subject. A composition is provided which comprises an enriched immune cell population reactive to a human endogenous retrovirus type E antigen on a tumor cell. A method of treating a neoplastic disease in a mammalian subject is provided which comprises administering to a mammalian subject a composition comprising an enriched immune cell population reactive to a human endogenous retrovirus type E antigen, in an amount effective to reduce or eliminate the neoplastic disease or to prevent its occurrence or recurrence.