Proprietary TCR candidate designed to recognize the oncogenic KRAS G12D mutation in the context of HLA-C08 expands CellentraTech’s precision oncology pipeline
CellentraTech, a biotechnology company developing next-generation in vivo gene therapy and precision immuno-oncology technologies, today announced the discovery and engineering of a proprietary KRAS G12D / HLA-C08-targeting T-cell receptor (TCR) candidate designed for highly selective recognition of cancer cells carrying the KRAS G12D oncogenic mutation.
The program is intended to create an immune receptor capable of distinguishing a KRAS G12D-derived tumor antigen presented by HLA-C08, providing a potential strategy for directing T cells against cancers driven by one of the most important oncogenic KRAS mutations.
The newly developed TCR candidate has advanced through CellentraTech’s computational discovery and structural evaluation workflow, where it demonstrated a favorable predicted target-recognition profile. The program is now advancing toward broader experimental validation, including functional activity, specificity, cross-reactivity and safety assessment.
Targeting One of Cancer’s Most Challenging Oncogenic Drivers
KRAS mutations are among the most consequential molecular drivers in human cancer. The G12D mutation occurs across multiple difficult-to-treat malignancies and has historically represented a challenging therapeutic target.
CellentraTech’s TCR strategy approaches KRAS G12D differently from conventional extracellular-targeted therapies.
Cancer cells continuously process intracellular proteins and display fragments of those proteins on their surface through HLA molecules. A properly engineered TCR can potentially recognize a mutation-derived peptide-HLA complex and thereby enable immune cells to distinguish tumor cells carrying a specific intracellular oncogenic mutation.
The CellentraTech candidate is engineered around this principle, targeting the intersection of:
KRAS G12D mutation → intracellular antigen processing → HLA-C08 presentation → mutation-selective T-cell recognition.
This approach could potentially expand immune targeting beyond conventional cell-surface antigens and provide access to oncogenic proteins that have historically been difficult to reach with antibody-based therapies.
Precision TCR Engineering
CellentraTech developed the candidate using an integrated computational and molecular-engineering workflow designed to optimize the geometry and selectivity of the interaction between the TCR and the tumor-associated peptide-HLA complex.
Development objectives include:
- strong recognition of the intended KRAS G12D / HLA-C08 complex;
- discrimination between mutant KRAS G12D and related normal peptide presentations;
- preservation of TCR recognition geometry associated with productive immune signaling;
- reduction of predicted off-target peptide-HLA interactions;
- systematic cross-reactivity and toxicity assessment; and
- compatibility with future engineered T-cell and in vivo immune-cell programming platforms.
The company believes this precision-recognition strategy could eventually support multiple therapeutic formats, including ex vivo engineered T-cell therapies as well as future in vivo T-cell programming approaches.
CTO Thomas: “We Want the Immune System to See the Mutation Itself”
Thomas, Chief Technology Officer of CellentraTech, said:
“KRAS G12D has been one of the defining challenges in precision oncology. Our goal was not simply to recognize a cancer cell—we wanted to design a T-cell receptor capable of recognizing the molecular consequence of the KRAS G12D mutation itself when it is presented by HLA-C08.”
Thomas continued:
“What excites us about this program is the possibility of turning an intracellular oncogenic mutation into an address that the immune system can recognize. Instead of being limited to proteins exposed on the exterior of a tumor cell, TCR technology gives us an opportunity to reach much deeper into cancer biology.”
“Our computational work indicates that we have identified a highly promising TCR architecture with the recognition characteristics we were seeking. The next critical step is comprehensive experimental validation. We intend to evaluate potency, mutant-versus-normal selectivity, cross-reactivity, functional T-cell activation and safety before making conclusions about therapeutic performance.”
Thomas added:
“Our long-term vision is larger than a single receptor. We are building a system in which cancer mutations can be identified, molecular recognition systems can be engineered against them, and those recognition systems can ultimately be delivered directly to immune cells. If successful, that framework could allow us to transform genomic information about a tumor into programmable immune recognition.”
Expanding the CellentraTech Oncology Platform
The KRAS G12D / HLA-C08 TCR program complements CellentraTech’s broader oncology portfolio, which combines TCR engineering, intracellular cancer targeting, nucleic-acid delivery and in vivo immune-cell programming.
CellentraTech is developing its TCR programs as part of a broader strategy to create a library of precision immune receptors capable of recognizing cancer-associated intracellular targets presented through HLA molecules.
Rather than viewing each receptor as an isolated therapeutic candidate, the company is developing a modular discovery framework intended to support future TCR programs across multiple oncogenic mutations and tumor-associated antigens.
Development Path
CellentraTech plans to advance the KRAS G12D / HLA-C08 candidate through a staged validation program addressing:
Target Recognition
Experimental confirmation of binding to the intended KRAS G12D / HLA-C08 complex.
Functional Activity
Evaluation of whether T cells expressing the candidate receptor selectively activate in response to appropriate target-positive cancer cells.
Mutation Selectivity
Assessment of discrimination between KRAS G12D and corresponding non-mutant or related peptide presentations.
Off-Target Screening
Broad evaluation of potentially cross-reactive human peptide-HLA complexes.
Safety Characterization
Testing designed to identify undesirable recognition of normal human cells and tissues.
Preclinical Translation
Subject to successful validation, evaluation in appropriate preclinical cancer models and future therapeutic-delivery configurations.
Potential Applications
If successfully validated, a KRAS G12D-directed TCR could ultimately be investigated in cancers in which the mutation and appropriate HLA presentation are present.
The program therefore represents a biomarker-defined precision oncology strategy, in which treatment eligibility would be determined not only by tumor type, but by the molecular mutation and HLA context of an individual patient’s cancer.
A Platform for Mutation-Directed Immunotherapy
CellentraTech believes the future of cancer immunotherapy will increasingly involve directing immune cells toward the molecular abnormalities that cause cancer rather than relying solely on broad tumor-associated markers.
The KRAS G12D / HLA-C08 program is an important step toward that objective.
“Cancer is fundamentally a disease of altered molecular information,” Thomas said. “Our objective is to give the immune system the ability to read that information with extraordinary precision. KRAS G12D is one example of what we believe can become a much broader generation of mutation-directed immune therapies.”
About CellentraTech
CellentraTech is a biotechnology company developing next-generation in vivo gene therapy, precision immuno-oncology and programmable therapeutic-delivery technologies.
The company’s research programs combine computational molecular design, engineered immune receptors, intracellular targeting, nucleic-acid therapeutics and advanced delivery technologies with the goal of creating new therapeutic modalities for cancer and other serious diseases.
CellentraTech — Make the World a Better Place.
Important Development Status
The KRAS G12D / HLA-C08 TCR described in this release is an investigational research-stage candidate. Computational findings do not establish clinical activity, safety or therapeutic efficacy. Experimental functional validation and additional preclinical development are required before conclusions regarding therapeutic potential can be made.
Forward-Looking Statements
This press release contains forward-looking statements concerning CellentraTech’s research programs, technology platforms, development plans and potential therapeutic applications. Such statements involve scientific, technical, regulatory and development risks and uncertainties. Computational, laboratory and preclinical findings may not predict subsequent results in humans. No investigational candidate described herein has been established as safe or effective for the treatment of cancer, and there can be no assurance that any candidate will successfully advance into or through clinical development.
