On September 28, 2021 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company engineering a novel class of injectable biologics to selectively engage and modulate targeted T cells directly within the patient’s body, reported the publication of research titled "Peptide-HLA-based immunotherapeutics platforms for direct modulation of antigen-specific T cells" in the peer-reviewed Nature journal, Scientific Reports (Press release, Cue Biopharma, SEP 28, 2021, View Source [SID1234608270]). The article describes Cue Biopharma’s IL-2 based CUE-100 series technology platforms, Immuno-STAT (Selective Targeting and Alteration of T cells) and Neo-STAT, being leveraged for the development of first-in-class biologics that enable selective activation of cancer-killing immune T cells within the patient’s body.

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"We believe our platforms address a significant challenge in immunotherapy of ensuring selective targeting of activation signals to anti-tumor T cells in the patient while sparing the indiscriminate systemic activation of the immune system," said Anish Suri, Ph.D., president and chief scientific officer of Cue Biopharma. "Adoptive cell therapy such as chimeric antigen receptor T-cell (CAR-T) therapies have demonstrated highly encouraging results for some patients but remain limited by the need of cellular ex-vivo manipulation and manufacturing challenges. Similarly, systemic approaches with immunostimulatory molecules, such as interleukin 2 (IL-2) or bispecific molecules, activate T cells indiscriminately and are associated with common severe adverse events, significantly limiting clinical benefit and applicability. Cue Biopharma’s approach and resulting platform, represents a potential breakthrough in the ability to selectively and safely modulate the immune system in a highly controlled and targeted manner directly in the patient’s body with the potential to create life-changing therapeutics with demonstrated improved efficacy and reduced toxicities."

Key aspects of Cue Biopharma’s technologies discussed in the article include:

The Immuno-STAT platform enables development of first-in-class off-the-shelf biologic molecules designed to selectively engage and activate disease-relevant T cells via the T cell receptors (TCR), mimicking the natural immune process, through the presentation of complimentary and synergistic signals, or "cues." An Immuno-STAT is engineered to include:
A first signal, or "cue" involving the presentation of a targeted and specific epitope, via a major histocompatibility (MHC)-peptide complex, to T cell receptors, or TCRs, of disease-specific T cells, to selectively engage a repertoire of T cells relevant to a particular disease such as cancer.
A corresponding second signal, or "cue" comprising the immunostimulant IL-2 molecule engineered with particular modifications for activation and expansion of CD8+ cytotoxic T cells, the relevant type of T cells with cancer-killing activity and minimize off-target binding and activation.
The Immuno-STAT is constructed upon a portion of a human antibody (the "Fc portion") that serves as the molecule’s backbone or scaffold and provides manufacturability and structural stability.
Through this design, Immuno-STATs enable disease specificity, targeted selective activation of CD8+ T cells and a larger therapeutic window for IL-2 effectiveness.
Neo-STAT is a plug-and-play variation of the Immuno-STAT platform designed with an empty "pocket" for the peptide presentation signal, enabling easy integration of disease-specific antigens a-posteriori to target a variety of cancers and infectious diseases.
The modular Immuno-STAT framework is compatible with diverse co-modulators, including immuno-suppressive molecules, with potential to address a variety of autoimmune diseases.
Ken Pienta, M.D., acting chief medical officer of Cue Biopharma, added, "We have identified a potential solution to safety and scalability challenges based on natural signals governing T cell function: peptide-HLA and costimulatory ligands, embodied in the Immuno-STAT and Neo-STAT immunotherapy platforms. The versatility and modularity of the platform as described in the paper, in addition to the clinical data to date supports the premise that our approach could be the next-generation solution to utilizing IL-2 as a targeted and selective immune activator for treating multiple cancers."

Cue Biopharma’s lead Immuno-STAT asset, CUE-101 has already shown encouraging results as a monotherapy in a Phase 1 dose escalation trial in late stage second line and beyond patients with HPV+ recurrent/metastatic head and neck cancer, which included a confirmed partial response with approximately 65% durable and ongoing tumor reduction and eight confirmed stable disease responses, controlling tumor growth for at least 12 weeks.

The Company is preparing for an Investigational New Drug filing for their next Immuno-STAT clinical candidate, CUE-102, which targets Wilms Tumor 1 (WT1), expressed in numerous solid tumors and hematological cancers.