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Open research questions in Monoclonal and Polyclonal Antibodies Research

124 unresolved questions extracted from the limitations and future-work sections of 411 Monoclonal and Polyclonal Antibodies Research papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • One of the challenges identified in the paper is the need to prevent Bet v 1 penetration into respiratory epithelial cells. Another challenge is the potential for nanobodies to dissociate from their targets, which could reduce their effectiveness. The paper also mentions the importance of preserving cell surface receptor integrity and preventing proteolytic degradation of ICAM-1 during experimental procedures.

    Bispecific nanobodies targeting Bet v 1 and ICAM-1 decrease respiratory epithelial penetration of Bet v 1 · 2026 · DOI

  • The study used a limited number of cell lines and allergens. The experiments were performed at specific temperatures (25 °C and 32 °C). The study did not investigate the long-term effects of bispecific nanobodies.

    Bispecific nanobodies targeting Bet v 1 and ICAM-1 decrease respiratory epithelial penetration of Bet v 1 · 2026 · DOI

  • The manual assembly of CSMs may present a challenge for large-scale production, - The trade-off between flexible deformability and load-bearing capacity remains a challenge for practical applications, - The intrinsic limitation on the load-carrying actuation in origami-inspired mechanisms remains a challenge

    A Drug‐Gated, Modular STAb‐T Immunotherapy With External Control · 2026 · DOI

  • The lack of robust, reversible mechanisms for externally controlling therapeutic activity in living cell therapies. The limitation of soft deployable robots is not clearly connected to the rest of the paper.

    A Drug‐Gated, Modular STAb‐T Immunotherapy With External Control · 2026 · DOI

  • The analysis of V(D)J usage, heavy-light pairing, and CDRH3 properties requires large datasets and sophisticated computational methods. The paper identifies the challenge of immune-context heterogeneity and productive-repertoire sampling in analyzing antibody repertoires. The study notes the limitation of not being able to perform a separate DH reading-frame analysis due to the lack of D-segment alignment coordinates.

    Recurrent antibody repertoire features associated with six selected human IGHV genes: V(D)J usage, heavy-light pairing, and CDRH3 properties · 2026 · DOI

  • further analysis of the IGHV locus, - investigation of the enzymatic history of individual sequences, - study of the structural interactions of CDRH3

    Recurrent antibody repertoire features associated with six selected human IGHV genes: V(D)J usage, heavy-light pairing, and CDRH3 properties · 2026 · DOI

  • Further evaluation of cevostamab in combination with other therapies, - investigation of the optimal dosing regimen for cevostamab, - assessment of the long-term safety and efficacy of cevostamab

    FcRH5×CD3 bispecific antibody cevostamab in relapsed or refractory multiple myeloma: a phase 1 trial · 2026 · DOI

  • Limited treatment options for relapsed or refractory multiple myeloma. Need for new therapies targeting FcRH5. Gap in understanding the safety and efficacy of cevostamab in this patient population.

    FcRH5×CD3 bispecific antibody cevostamab in relapsed or refractory multiple myeloma: a phase 1 trial · 2026 · DOI

  • Antibody language models learn from large natural repertoires, but whether generic representations capture the constraints of specialized antibody formats remains unclear.

    A foundation model learns the sequence and functional grammar of fully human heavy-chain-only antibodies · 2026 · DOI

  • Although pigs are increasingly used as translational models for therapeutic antibody evaluation, the interactions between porcine Fc receptors (pFcγRs) and porcine (pIgG) or human IgG (hIgG) subclasses remain poorly defined.

    Human and porcine IgG subclasses differentially engage porcine Fc receptors · 2026 · DOI

  • The clinical benefit of therapies targeting the KRAS G12C mutation is substantially limited by the development of resistance through multiple mechanisms.

    KRAS Inhibitor–Induced Cancer Cell Death Enhances Sensitivity to Immune-Mediated Bystander Killing of Drug-Resistant Subclones · 2026 · DOI

  • Human immunoPET, fluorescence window studies, quantitative tissue imaging, and single-cell spatial pharmacobiology show substantial heterogeneity across lesions and cells, whereas lesion-level exposure–outcome evidence remains limited.

    Spatial PK–PD mismatch in tumor-targeting antibodies and ADCs: from lesion access to pharmacologic execution · 2026 · DOI

  • While the functional significance of FcγRIIB is well established in mice, its physiological roles and the regulatory mechanisms governing its expression remain incompletely understood in humans.

    The ETS-family transcription factor PU.1 is a critical regulator of the inhibitory Fcγ receptor IIB expression in humans · 2025 · DOI

  • While antibody-induced clustering of FcγRIIIa (CD16a) is thought to drive ADCC, the molecular basis for this activity has not been fully described.

    CD16a pairs form the basal molecular subunit for the NK-cell ADCC lytic synapse · 2025 · DOI

  • In particular, the pharmacological properties of monobodies, including plasma stability, toxicity and pharmacokinetics have not been investigated.

    Improving the pharmacokinetics, biodistribution and plasma stability of monobodies · 2024 · DOI

  • Despite their use as basic research tools, the potential of monobodies as protein therapeutics remains to be explored.

    Improving the pharmacokinetics, biodistribution and plasma stability of monobodies · 2024 · DOI

  • Nanobodies, which represent the next generation of antibodies due to their unique properties, face a significant limitation in their poor physical adsorption on solid supports.

    Novel Polystyrene-Binding Nanobody for Enhancing Immunoassays: Insights into Affinity, Immobilization, and Application Potential · 2024 · DOI

  • The fragmentation of the toolchain in computational protein design. The need for high-level computational expertise to access and utilize specialized tools.

    ProteinMCP: An Agentic AI Framework for Autonomous Protein Engineering · 2026 · DOI

  • The lack of automation in computational protein engineering workflows. The need for a platform that can accelerate and democratize protein engineering.

    ProteinMCP: An Agentic AI Framework for Autonomous Protein Engineering · 2026 · DOI

  • The formation of insoluble aggregates known as inclusion bodies during protein expression. The need for efficient refolding methods to obtain functional protein. The challenge of improving protein recovery yields.

    Investigation of the Effect of Arginine and Glutathione on Recovery of a Single Domain Antibody Produced in Bacteria in Inclusion Bodies · 2026 · DOI

  • The study did not explore alternative expression systems or modifications to the existing protocols. The yield of pure protein was less than 1mg per liter of culture, indicating the need for purification optimization.

    Investigation of the Effect of Arginine and Glutathione on Recovery of a Single Domain Antibody Produced in Bacteria in Inclusion Bodies · 2026 · DOI

  • Limited understanding of the potential effects of YTE substitutions on Fc-mediated functions - Limited understanding of the risk of immunogenicity - Limited understanding of differences in FcRn binding across species

    YTE-engineered antibodies: From neonatal Fc receptor binding mechanisms to next-generation therapeutics · 2026 · DOI

  • The immune system's ability to recognize and neutralize pathogens is not fully understood. The process of affinity maturation trajectories for antibodies is complex.

    Taking the biology seriously makes models better · 2026 · DOI

  • Limited discriminative performance of Boltz-2 confidence metrics. Difficulty in distinguishing true binding from non-binding pairs at scale. Need for effective computational interaction prediction methods.

    Benchmarking Boltz-2 for Screening of Therapeutic Antibody-Antigen Interactions · 2026 · DOI

  • The study focuses on a specific problem of AB-AG discrimination. The dataset is limited to 519 monoclonal antibodies from Thera-SabDab. The paper does not explore other potential applications of Boltz-2.

    Benchmarking Boltz-2 for Screening of Therapeutic Antibody-Antigen Interactions · 2026 · DOI

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124 open questions have been extracted from the limitations and future-work passages of 411 Monoclonal and Polyclonal Antibodies Research papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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