Immunogenic Brachyury Polypeptides for Broad Cancer Diagnosis and Treatment
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Solution Overview
Problem
Current cancer therapies lack effective antigens for diagnosing and treating various types of cancers, particularly those beyond prostate cancer, as existing immunotherapies rely on limited tumor-associated antigens, necessitating the identification of additional antigens for broader cancer treatment applications.
Innovation Solution
The use of immunogenic Brachyury polypeptides, specifically those expressed in human tumors like those in the small intestine, stomach, kidney, bladder, uterus, ovary, and testes, along with nucleic acids and viral vectors encoding these peptides, to induce an immune response and diagnose Brachyury-expressing cancers, combined with methods involving B7-1, B7-2, and cytokines for enhanced therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If existing immunotherapies rely on limited tumor-associated antigens, then the treatment approach is simple and well-established, but the applicability is restricted to specific cancer types only
Solution Approach 1:
The patent identifies Brachyury as a universal tumor-associated antigen expressed across multiple cancer types including prostate, lung, colon, kidney, bladder, uterus, ovary, and testicular cancers. This single antigen serves multiple therapeutic applications across diverse malignancies, resolving the contradiction by providing broad cancer type applicability without requiring separate antigen identification processes for each cancer type
2Adaptability or versatility
If new tumor-associated antigens are identified for broader cancer treatment, then the versatility increases, but the complexity of antigen identification and validation increases
Solution Approach 1:
The patent performs preliminary identification and validation of Brachyury as a tumor-associated antigen through in-silico screening and experimental verification before clinical application. Expression analysis was conducted across multiple cancer cell lines and tumor samples, confirming Brachyury overexpression in various carcinomas. This preliminary characterization simplifies subsequent detection and therapeutic development, as the antigen's expression patterns and immunogenicity are already established
Data Source
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AI summary
It is disclosed herein that Brachyury is expressed in human tumors, specifically in tumors of the small intestine, stomach, kidney, bladder, uterus, ovary, and testes, as well as in lung, colon and prostate carcinomas. Immunogenic Brachyury polypeptides are disclosed herein. These polypeptides can be used in diagnostic assays for Brachyury expression, as well as for inducing an immune response to Brachyury. Polynucleotides encoding the immunogenic Brachyury polypeptides, vectors including these polypeptides, host cells transformed with these vectors, and methods of using these polypeptides, polynucleotides, vectors, and host cells are provided. Methods of diagnosing a Brachyury-expressing cancer are also provided. Exemplary cancers include small lung, colon, intestine, stomach, kidney, bladder, uterus, ovary, and testes and prostate cancers. Methods of treating cancer are also disclosed.