Anti-CD103 Antibodies for Tumor-Infiltrating T Cell Targeting
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Solution Overview
Problem
Existing cancer immunotherapies targeting immune checkpoint pathways, such as those using antibodies against CTLA-4 and PD-1/PD-L1, often fail to stimulate a productive antitumor response due to limited T cell infiltration into tumor environments, highlighting the need for a comprehensive understanding of cancer-specific lymphocytes like CD103+ tumor-infiltrating T cells.
Innovation Solution
Development of anti-CD103 antibodies and antigen binding fragments that specifically target human CD103, with varying CDR sequences to enhance T cell interaction with tumor cells, potentially improving immunotherapy efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If checkpoint inhibitors (anti-CTLA-4, anti-PD-1/PD-L1 antibodies) are used to treat cancer, then immune response is activated, but T cell infiltration into tumor environment remains limited
Solution Approach 1:
The patent introduces CD103 as a new target marker that serves as an intermediary to identify and recruit T cells with tumor-killing potential. By targeting CD103+ T cells specifically, the invention creates a bridge between checkpoint inhibition and effective T cell infiltration, thereby resolving the contradiction between activating immune response and achieving sufficient T cell infiltration into the tumor microenvironment.
2Quantity of substance
If T cells accumulate in tissues surrounding the tumor mass, then T cell presence increases, but interaction with tumor cells themselves is insufficient
Solution Approach 1:
The patent applies local quality by specifically targeting CD103+ T cells rather than all T cells. This selective approach ensures that only T cells with the appropriate functional phenotype (those capable of effective tumor interaction) are recruited and activated at the tumor site, thereby improving the quality of T cell-tumor cell interactions rather than merely increasing overall T cell quantity.
3Reliability
If checkpoint inhibition is applied to cancer therapy, then some clinical benefit is achieved, but majority of patients fail to respond
Solution Approach 1:
The patent changes the parameter of T cell identification from general checkpoint markers to the specific CD103 marker. This parameter change enables better patient selection and treatment adaptation, as CD103+ T cells represent a specific subset with proven tumor-killing activity. By targeting this specific population, the invention expands the adaptability of immunotherapy to accommodate diverse patient responses and improve overall treatment efficacy.
Data Source
AI summary
The present invention relates to anti-CD 103 antibodies, as well as use of these antibodies in diagnosis, prognosis, monitoring, and treatment of diseases. Also disclosed is an imaging agent comprising the anti-CD 103 antibody and a detectable label, wherein the antibody either does not block CD 103 binding to E-cadherin or at least partially blocks CD 103 binding to E-cadherin. The methods of treatment involve administering the anti CD 103 antibody which may be optionally coupled to a cytotoxic agent. Diseases to be treated include e.g. Hairy Cell leukemia, HCLv, intestinal and extraintestinal lymphomas, enteropathy-associated T-cell lymphoma (EATL), T-lymphoblastic leukemia/lymphoma (T-ALL), T-cell prolymphocytic leukemia (T-PLL), adult T cell leukemia/lymphoma (ATLL), mycosis fungoides (ME), anaplastic large cell lymphoma ALCL, cutaneous T-cell lymphoma (CTCL), Sezary Syndrome (SS), Alzheimer's disease, Parkinson's disease or multiple sclerosis.