Multi-Peptide MHC Targeting: How Deck Bio Is Broadening T Cell Engager Access in Solid Tumors

Speaking with BioPharm International® at the 2026 BIO International Convention (BIO 2026), which occurred June 22–25 in San Diego, Johanna K. Kaufmann, PhD, chief scientific officer of Deck Bio, a Cambridge, Mass.-based pre-seed-stage oncology startup, discussed the company’s development of novel T cell engagers for solid tumors. Dr Kaufmann highlighted Deck Bio's approach to the longstanding challenges of target scarcity and tumor heterogeneity in solid tumor TCE development, and the company's lead program, DBXO-1.

BioPharm: What is Deck Bio's focus, and what differentiates its approach in the T cell engager space?

Dr Kaufmann (Deck Bio): Deck Bio is developing novel T cell engagers for solid tumors. The core challenge we address is that, in solid tumors, T cell engagers have so far been restricted to niche indications‚ primarily because of the scarcity of appropriate cell surface targets and much more pronounced tumor heterogeneity compared to hematologic malignancies, which drives resistance mechanisms.¹

We are selecting a next-generation target class, and that is peptide major histocompatibility complex (pMHC) complexes. These are generated as part of natural immune surveillance mechanisms of the body and display a sample of intracellular proteins on the cell surface, making them accessible to a biologic like a T cell engager. We can therefore select targets expressed very tumor-exclusively, avoiding residual healthy tissue expression and the resulting toxicity liabilities that are particularly problematic for a high-potency modality like T cell engagers.² Through pMHC targeting, we follow in the footsteps of tebentafusp (Kimmtrak; Immunocore), which received FDA approval for uveal melanoma in January 2022.³ We take the approach to the next level with our major point of differentiation: multi-peptide MHC targeting.

What is multi-peptide MHC targeting, and how does it address tumor heterogeneity and antigen escape?

We identify signatures of multiple target proteins that derive peptides identical or highly similar to each other, such that they load into the same HLA [human leukocyte antigen] allele and can be recognized by a single drug. The stacking effect of expressing multiple target proteins significantly increases copy number at the cell surface‚ meaning more patients meet the expression threshold required for response. This addresses market access barriers, where patients are typically stratified by both HLA typing and target expression, substantially restricting the eligible population.

These target proteins are independently regulated transcriptionally, so a tumor or lesion would have to lose expression of multiple independent proteins to escape‚ making antigen loss more difficult.⁴ In a priority indication for our lead program DBXO-1, non-small cell lung cancer (NSCLC), multi-targeting more than doubles the number of patients in analyzed cohorts that meet an expression threshold estimated to drive clinical response as compared to a single-target approach with a very popular pMHC target.

What are the priority indications for DBXO-1, and what technology platforms support it?

Our priority indications are NSCLC, gastroesophageal cancer, head and neck cancer, and liver cancer because 30 to 50% of patients with these tumor types express our target signature at sufficient levels. They are also relatively well-immune-infiltrated tumors, which increases our likelihood of success for a first proof-of-concept.

On the platform side, specificity is ensured through dbScope, a comprehensive, sequence-agnostic workflow that tests binder reactivity against any peptides displayed in the HLA type of interest in healthy tissues. For DBXO-1 targeting a signature in HLA-A*02:01, [more than] 13,500 peptides have been detected by mass spectrometry to be displayed in that allele across healthy organs. When we run our lead binders through dbScope, we see a residual binding profile comparable to tebentafusp‚ which is encouraging for our current leads.

Our T cell engager platform [dbTCE] engages pMHC complexes using a stabilized soluble T cell receptor rather than a TCR-mimetic antibody fragment. Historically, soluble TCRs have suffered from low manufacturing yields and poor stability; we have identified a proprietary stabilization technology that brings the profile into ranges more comparable to monoclonal antibodies, potentially enabling lower-risk manufacturing and, if the data support it, subcutaneous administration.

Where is Deck Bio in its development timeline, and what does success look like at 2 and 5 years?

We are in preclinical stage, developing our development candidate for DBXO-1 by end of 2026 with a planned clinic entry in early 2028. Two-year success means a cleared IND [investigational new drug] and efficient patient enrollment‚ including navigating HLA typing requirements. Five-year success is clinical proof-of-concept, which means an appropriate safety profile and efficacy signal in a selected patient population, with a clear development plan to advance to phase 2 and phase 3.

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References

1. Cao L, Leclercq-Cohen G, Klein C, Sorrentino A, Bacac M. Mechanistic insights into resistance mechanisms to T cell engagers. Front. Immunol. 2025;16:1583044. doi:10.3389/fimmu.2025.1583044

2. Garcia-Lorenzo E, Dorta M, Doger B, Pedregal M, Moreno V. Landscape of T-cell engagers in solid tumors. Oncologist. 2026;31(5):oyag129. doi:10.1093/oncolo/oyag129

3. FDA. BLA 761228 Approval. Published January 25, 2022. Accessed June 22, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2022/761228Orig1s000ltr.pdf

4. Mungalov RV, Mushenkova NV, Chudakov DM, Turchaninova MA. Engaging T cells for cleanup. Front. Immunol. 2025;16:1551424. doi:10.3389/fimmu.2025.1551424