Proprietary T-cell receptor program is designed to recognize the shared oncogenic KRAS G12C neoantigen through a defined peptide-HLA complex, expanding the company’s precision immuno-oncology pipeline
Cellantra, an in vivo gene therapy and next-generation immuno-oncology biotechnology company, today announced the discovery and invention of a novel T-cell receptor (TCR) candidate directed against the oncogenic KRAS G12C mutation, a recurrent cancer driver found across multiple solid tumors.
The newly developed program is designed to recognize a KRAS G12C-derived neoantigen presented by a defined human leukocyte antigen (HLA) class I molecule on the surface of tumor cells. The lead HLA restriction and receptor configuration are being maintained as proprietary while Cellantra advances intellectual-property protection, experimental confirmation and comprehensive specificity testing.
KRAS is an intracellular signaling protein. TCR-based therapies can potentially access this class of target because intracellular proteins are processed into short peptides that can be displayed by HLA molecules at the cell surface. Published research has independently demonstrated presentation and T-cell recognition of oncogenic KRAS neoantigens, including KRAS G12C, across defined HLA-I contexts, supporting the biological rationale for development of mutation-directed TCR therapies.
A Mutation-Specific TCR Program Designed Around KRAS G12C
Cellantra developed the KRAS G12C TCR program using its integrated computational immunology, peptide-HLA modeling, structural evaluation and protein-engineering platform. The program is intended to produce a receptor that combines strong functional recognition of the mutant peptide-HLA complex with strict discrimination from the corresponding wild-type KRAS sequence and unrelated human peptides.
The lead candidate has progressed through the company’s discovery and structural-prioritization stage. Cellantra is advancing the receptor through experimental peptide-HLA binding confirmation, T-cell functional testing, mutation selectivity, antigen-density sensitivity, cross-reactivity analysis and broader safety assessment before determining readiness for formal preclinical development.
The program is being developed around several core objectives:
- selective recognition of the intended KRAS G12C-derived peptide-HLA complex;
- strong functional activity compatible with efficient T-cell activation at disease-relevant antigen density;
- discrimination between mutant KRAS G12C and the corresponding wild-type KRAS peptide;
- systematic assessment of related KRAS hotspot variants, homologous human peptides and other potential off-target peptide-HLA complexes;
- confirmation that receptor performance depends on the intended HLA restriction and target peptide context; and
- compatibility with engineered TCR-T cells and future in vivo immune-cell programming strategies.
A Shared Oncogenic Driver Accessible to TCR-Based Immunotherapy
KRAS G12C is a defined amino-acid substitution in a major oncogenic driver protein. Because the mutation creates a sequence difference that is absent from wild-type KRAS, it can generate a tumor-associated neoantigen when appropriately processed and presented by HLA molecules. This creates a potential route for immune recognition directed at the cancer-driving mutation itself rather than at an unrelated surface marker.
External studies have identified multiple mutant KRAS peptide-HLA targets and have shown that KRAS-specific T cells and TCRs can recognize endogenously processed mutant KRAS in tumor-cell systems. More recent work has expanded the available KRAS G12C TCR landscape across HLA-A3-family presentation contexts. Cellantra’s program is being developed independently as a proprietary receptor discovery and engineering effort.
“KRAS G12C represents the type of target we believe TCR technology is uniquely positioned to address: an intracellular, genetically defined cancer driver that can be converted into a highly specific immune-recognition signal through peptide-HLA presentation,” the company said. “Our objective is to engineer a receptor with the functional strength required for tumor recognition while maintaining a disciplined focus on mutant selectivity, HLA restriction and comprehensive off-target assessment.”
Potential Applications in Engineered and In Vivo T-Cell Programming
The initial application of the KRAS G12C receptor is intended to support engineered TCR-T cells in which T cells are programmed to express the candidate receptor and recognize tumor cells displaying the defined KRAS G12C peptide-HLA complex.
If the candidate meets the company’s functional and safety criteria, Cellantra also intends to evaluate its compatibility with future in vivo gene-delivery systems designed to program therapeutic T cells directly inside the body.
Such an approach could potentially combine mutation-specific molecular recognition with targeted nucleic-acid delivery, regulated receptor expression and additional cellular-control technologies. These applications remain exploratory and will depend on successful validation of receptor specificity, functional activity, delivery performance and safety.
Advancing Through Specificity, Cross-Reactivity and Preclinical Validation
Cellantra will next focus on orthogonal confirmation of target binding, T-cell activation, cytokine response, tumor-cell recognition and cytotoxic function, together with comprehensive off-target assessment.
Planned specificity studies are expected to evaluate wild-type KRAS, related KRAS hotspot mutations, human peptides with sequence or structural similarity to the intended neoantigen, and relevant HLA backgrounds.
The company intends to use these studies to determine whether the candidate meets internal criteria for advancement into broader preclinical development, including disease-relevant tumor models, manufacturability assessment, safety testing and integration with the company’s engineered-cell and in vivo gene-therapy platforms.
The KRAS G12C TCR candidate is investigational and has not been approved for therapeutic use. Its clinical safety and efficacy have not been established. The HLA restriction and molecular configuration of the lead candidate remain undisclosed, and no statement in this release should be interpreted as evidence of clinical benefit.
About Cellantra
Cellantra is a biotechnology company developing next-generation in vivo gene therapy and precision immuno-oncology technologies. The company is building a pipeline spanning engineered T-cell receptor programs, intracellular cancer-targeting therapeutics, in vivo immune-cell programming and advanced nucleic-acid delivery technologies.
Cellantra’s research strategy combines computational molecular design, target discovery, protein engineering, targeted delivery and experimental validation with the long-term objective of transforming complex biological discoveries into programmable therapeutic modalities.
Cellantra – Make the World a Better Place.
Forward-Looking Statements
This press release contains forward-looking statements regarding Cellantra’s KRAS G12C TCR program, research programs, technology platforms, intellectual-property strategy, development plans and potential therapeutic applications. These statements involve scientific, technical, regulatory and development uncertainties. Computational results, discovery-stage characterization and early preclinical findings may not predict subsequent experimental, preclinical or clinical outcomes. TCR-based therapies can present risks including inadequate antigen presentation, HLA restriction, immune escape, insufficient tumor activity and unintended peptide cross-reactivity. Cellantra’s investigational programs have not been demonstrated to be safe or effective in humans, and no assurance can be given that any program will successfully advance into or through clinical development.
