Novel T-cell receptor program is designed to selectively recognize the shared oncogenic KRAS G12V neoantigen presented by HLA-A*11:01, expanding the company’s precision immuno-oncology and programmable T-cell pipeline
Cellantra
, an in vivo gene therapy and next-generation immuno-oncology biotechnology company, today announced the discovery and engineering of a novel, potent T-cell receptor (TCR) candidate directed against the oncogenic KRAS G12V mutation in the context of HLA-A*11:01.
The newly developed TCR is designed to recognize a KRAS G12V-derived neoantigen presented by HLA-A11:01 on the surface of tumor cells. KRAS G12V is a recurrent driver mutation found across multiple solid tumors, while HLA-A11:01 provides a defined antigen-presentation context for TCR-based recognition. This combination creates a mutation-specific therapeutic address that may allow engineered T cells to distinguish KRAS G12V-positive cancer cells from cells presenting the corresponding wild-type KRAS sequence.
Peer-reviewed research has independently established that KRAS G12V-derived peptides can be processed and presented by HLA-A*11:01 and recognized by antigen-specific TCRs, providing a strong biological foundation for further development of this target class.
A Potent TCR Candidate Designed for Mutant-Selective Recognition
Cellantra
developed the KRAS G12V/HLA-A11:01 program through its integrated computational immunology, structural modeling and protein-engineering platform. The program is designed to combine high functional potency with strict dependence on both the mutant KRAS peptide and the HLA-A11:01 restriction element.
The lead candidate has been prioritized as a potent discovery-stage TCR based on the company’s integrated design criteria. Cellantra
is advancing the candidate through experimental binding, cellular activity, specificity, peptide cross-reactivity and safety studies before determining readiness for formal preclinical development. The term “potent” in this release refers to the intended discovery-stage functional profile of the engineered candidate and does not imply established clinical efficacy.
The program is being developed around several core objectives:
- potent recognition of the intended KRAS G12V peptide-HLA-A*11:01 complex at disease-relevant antigen density;
- strict discrimination between mutant KRAS G12V and corresponding wild-type KRAS peptide-HLA complexes;
- dependence on HLA-A*11:01 to support a clearly defined, genetically addressable patient population;
- systematic assessment of homologous human peptides, related KRAS variants and other potential cross-reactive peptide-HLA complexes;
- functional compatibility with engineered T-cell therapy and future in vivo immune-cell programming strategies; and
- a development path that integrates molecular potency with off-target risk reduction rather than affinity enhancement alone.
Targeting an Intracellular Cancer Driver Through the HLA System
KRAS is an intracellular signaling protein and cannot be targeted by conventional surface-antigen recognition in the same manner as many antibody or CAR-based therapies. TCR-based approaches can instead recognize short peptides generated from intracellular proteins after cellular processing and presentation by HLA molecules on the cell surface.
For KRAS G12V-positive tumors, this creates an opportunity to direct immune recognition toward the mutated driver itself rather than an unrelated surface marker. The strategy may be particularly relevant in solid tumors where highly selective extracellular targets are limited or heterogeneous.
“The KRAS G12V/HLA-A11:01 program reflects our goal of engineering TCRs against genetically defined cancer drivers with the potency, selectivity and safety discipline required for precision cell therapy,” the company said. “KRAS G12V is especially compelling because the mutation creates a tumor-specific neoantigen, while HLA-A11:01 provides a defined molecular context for immune recognition. Our focus now is to establish that potency is accompanied by rigorous mutant selectivity and a clean cross-reactivity profile.”
Potential Applications Across Engineered and In Vivo T-Cell Platforms
The initial development path for the candidate is intended to support engineered TCR-T cells in which patient or donor T cells are programmed to express the KRAS G12V-specific receptor. If the candidate satisfies the company’s specificity and safety criteria, Cellantra
also intends to evaluate its compatibility with future in vivo gene-delivery systems designed to program T cells directly inside the body.
A modular KRAS G12V TCR could potentially be paired with additional cellular-control technologies, including regulated expression, persistence tuning, logic-gated activation and combination strategies designed to address the immunosuppressive tumor microenvironment. These applications remain exploratory and will depend on successful preclinical validation.
Building Toward Experimental and Preclinical Validation
Cellantra
will next focus on orthogonal confirmation of peptide-HLA binding and recognition, functional T-cell activation, tumor-cell recognition, antigen-density sensitivity and comprehensive off-target assessment. Cross-reactivity screening will include wild-type KRAS, related KRAS mutant peptides and human peptides with sequence or structural similarity to the intended neoantigen.
Cross-reactivity is an important development consideration for this target class; recent work has specifically evaluated potential recognition of homologous self-peptides by HLA-A*11:01-restricted KRAS G12V TCRs.
The company intends to use these studies to determine whether the candidate meets internal criteria for advancement into broader preclinical development, including safety testing, manufacturability assessment and evaluation in disease-relevant tumor models.
The KRAS G12V/HLA-A*11:01 TCR candidate is investigational and has not been approved for therapeutic use. Clinical safety and efficacy have not been established. No statement in this release should be interpreted as evidence that the candidate will successfully enter or complete clinical development.
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 G12V/HLA-A*11:01 TCR program, research programs, technology platforms, 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 tumor recognition, HLA restriction, immune escape 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.
