Atreca is a biotechnology company focused on developing cancer immunotherapies by exploring the body’s defense mechanisms. The company identifies specific anti-tumor immune responses that occur naturally in cancer patients who have experienced positive clinical outcomes. By isolating these successful immune components, Atreca seeks to translate them into novel therapeutic candidates that harness the immune system’s power against solid tumors.
The Immune Repertoire Capture Platform
The foundation of Atreca’s discovery engine is its proprietary Immune Repertoire Capture (IRC) platform. This technology identifies and isolates the most effective, naturally occurring immune responses in cancer patients. The platform operates by analyzing the active immune system at the single-cell level, specifically targeting the B-cells and T-cells of individuals who have demonstrated a robust anti-tumor response.
The IRC platform employs next-generation sequencing to capture the full, natively paired variable regions of both antibodies and T-cell receptors (TCRs) expressed by selected immune cells. Capturing the full sequence of these receptors provides the exact molecular blueprint the body used to recognize the tumor. This method bypasses the limitations of traditional drug discovery, which typically searches for a tumor target before identifying a corresponding therapeutic molecule.
The technology simultaneously identifies both the therapeutic molecule, such as a potent TCR, and its corresponding tumor antigen, without prior knowledge of the antigen. This strategy yields a library of highly specific TCRs and antibodies that are proven to be functional and tumor-selective in a human setting. Focusing on these naturally occurring T-cell responses from “elite responders” allows Atreca to rapidly advance candidates with a higher probability of clinical benefit.
Developing Novel T-Cell Receptor Therapies
The T-cell receptor sequences and tumor targets identified through the IRC platform serve as the intellectual property for developing next-generation therapeutics. While the platform identifies TCRs, Atreca’s clinical strategy focuses on developing T-cell-related modalities like bispecific T-cell engagers. These engagers are engineered molecules that leverage the specificity of discovered tumor targets to redirect the patient’s existing T-cells toward the tumor.
A prominent example is the preclinical candidate APN-346958, a bispecific T-cell engager developed with Xencor. This molecule has two distinct binding sites: one attaches to a novel tumor-associated antigen (a ribonucleoprotein identified by the IRC platform), and the other binds to the CD3 co-receptor on the surface of a T-cell. This dual-binding action forms an artificial bridge, or synapse, between the T-cell and the cancer cell.
Once the engager connects the two cells, it forces the T-cell to activate and release cytotoxic molecules, such as perforin and granzymes, which destroy the tumor cell. This mechanism activates a patient’s T-cells to attack a specific tumor antigen, even if those T-cells would not normally recognize the antigen on their own. The target for APN-346958 is expressed on over 50% of samples in several solid tumor types, including colorectal, thyroid, and head and neck cancers, demonstrating the platform’s ability to discover widely expressed tumor-specific antigens.
Current Status of Clinical Programs
Atreca’s most advanced clinical candidate, the monoclonal antibody ATRC-101, had been evaluated in a Phase 1b trial for patients with various advanced solid tumors. The study progressed through dose escalation and expansion cohorts, including evaluating the therapy in combination with the checkpoint inhibitor pembrolizumab. Data from the trial indicated that ATRC-101 was generally well-tolerated across the doses tested.
Preliminary efficacy findings suggested that patients with high expression of the target antigen experienced longer progression-free survival. However, in 2023, the company suspended the development of ATRC-101. This decision was driven by financial conditions and a pivot to focus resources on its earlier-stage preclinical pipeline.
The company’s T-cell related programs, including the bispecific T-cell engager APN-346958, are currently in the preclinical stage of development. Atreca is advancing this candidate through Investigational New Drug (IND)-enabling studies. The goal is to submit an IND application to the U.S. Food and Drug Administration in early 2025. This represents the future direction of the platform’s product development efforts.