The speed at which the immunotherapy landscape has pivoted into autoimmunity shows no sign of slowing as we move through 2026. What began as a trickle of exploratory programmes has become a sustained influx of customer requests looking to test new and existing therapeutics to determine their impact upon immune dysregulation. At RoukenBio, this shift is material: we’re seeing a marked rise in requests for human‑relevant functional assays across multiple autoimmune indications and mechanistic classes, from T cell attenuation and B cell targeting to Treg modulation, antigen‑specific responses and myeloid‑driven inflammation. The breadth of these enquiries reflects a sector that is no longer testing the waters but actively building the next generation of autoimmune therapeutics and turning to advanced assay systems to guide those decisions with confidence.

Autoimmunity and the Evolving Immunotherapy Landscape

Autoimmune diseases encompass more than 80 distinct clinical conditions; however, the therapeutic landscape is largely shaped by six major indications: rheumatoid arthritis (RA), inflammatory bowel disease (IBD), psoriasis, multiple sclerosis (MS), systemic lupus erythematosus (SLE) and type 1 diabetes (T1D).  These conditions attract the bulk of clinical investment due to their high prevalence, chronic morbidity and substantial economic burden. However, interest is steadily broadening toward less common autoimmune disorders. Although these rarer diseases have small patient populations, they often feature well‑defined immune drivers and few effective therapies, making them attractive for demonstrating clear proof of mechanism. Their biology can be shaped by a single dominant pathway or autoantibody, enabling smaller and faster clinical studies, reduced competition, and the potential for expedited regulatory paths.

Across autoimmune diseases, clinical presentation can vary widely, but the underlying immunopathology frequently converges on shared mechanisms: overactive T cell responses, pathogenic B cell activity, impaired regulatory networks, and dysregulated cytokine signalling. This mechanistic overlap explains why therapies developed for one disease often show utility in others. Cytokine modulators targeting pathways such as TNF‑α, IL‑6, IL‑17, and IL‑23 illustrate this well: initially advanced in conditions like RA or psoriasis, these interventions have since proven relevant across a spectrum of autoimmune settings driven by similar inflammatory circuits.

Against this backdrop, developers face a strategic choice between pursuing broad, cross‑disease mechanisms or creating therapies tailored to the unique biology of a specific condition. Pathway‑agnostic approaches, focusing on core immunological processes such as T cell activation, B cell survival, or regulatory cell function, offer the advantage of applicability across multiple indications, expanding both clinical reach and commercial potential. In contrast, disease‑specific programs that target organ‑restricted autoantigens or narrow inflammatory pathways can deliver differentiated benefit in settings where generalised strategies fall short. Together, these options give companies the flexibility to balance scientific ambition with unmet medical need, whether by addressing shared mechanisms across autoimmune diseases or by developing precise, high‑impact treatments for patients with highly defined, underserved conditions.

Evolving Modalities in Autoimmune Immunotherapy

Advances in immuno‑oncology over the past decade have reshaped our ability to engineer and control immune responses, and many of these same modalities now map seamlessly onto autoimmune disease. The very tools built to overcome immune tolerance in cancer, such as CAR‑T cells, bispecific engagers, and next‑generation antibody formats, can be repurposed to restore tolerance in autoimmunity by selectively removing or reprogramming pathogenic immune subsets. This translational momentum has opened the door to a new therapeutic era where I/O‑bred platforms are adapted to reset, rather than activate, the immune system. At the same time, entirely new modalities, ranging from precision small molecules to engineered regulatory cell therapies are expanding the landscape further, offering increasingly targeted ways to disrupt autoimmune pathology without broad immunosuppression.

Cell‑Based Therapies

Cell‑based immunotherapies, particularly CAR‑T cells, have demonstrated compelling potential for the treatment of severe autoimmune diseases. Early‑phase clinical studies show that CD19‑directed CAR‑T cells can selectively eliminate autoreactive B cells, resulting in sustained, drug‑free remission in conditions including SLE, RA, systemic sclerosis, and myasthenia gravis. By depleting the autoantibody‑producing B cell compartment that underpins disease pathology, these therapies disrupt the self‑perpetuating cycle of immune activation and inflammation, enabling durable immune reset. Consistent with this mechanism, ongoing Phase I–III trials across multiple autoimmune indications report encouraging efficacy alongside favourable safety profiles. 

Beyond classical CAR‑T, next‑generation engineered cell therapies are rapidly broadening the therapeutic possibilities in autoimmunity. CAR‑T constructs express autoantigens on their surface enabling them to selectively seek out and eliminate the exact autoantibody‑producing B cell clones that drive disease. In parallel, CAR‑Treg platforms are being designed to actively re‑establish immune tolerance; by redirecting regulatory T cells to inflamed tissues with the aim to modulate immune activity. Both these approaches offer a more nuanced way to restore balance without broad immunosuppression. 

Monoclonal Antibodies

Monoclonal antibodies remain central to autoimmune therapy, with newer candidates engineered for more precise immune modulation. Unlike oncology, where PD‑1/PD‑L1 blockade enhances immunity, autoimmune pipelines increasingly focus on checkpoint agonism to dampen hyperactive T cell responses and restore tolerance. Agents such as rosnilimab and peresolimab illustrate this strategy, reducing T cell activation and inflammatory cytokines while improving regulatory balance.

In parallel, other targeted antibody classes continue to expand the therapeutic landscape, including BAFF‑R blockers, IL‑17/IL‑23 pathway modulators, and FcRn inhibitors, each aiming for selective, durable recalibration of dysregulated immunity across diseases such as IgA nephropathy, Sjögren’s disease, and SLE. T cell–depleting antibodies provide rapid debulking of pathogenic effector populations in severe or early autoimmune disease. Broad agents such as anti‑CD52 remove wide lymphocyte compartments, while more selective approaches, such as targeted depletion of T cells expressing particular α/β chains allow for a more disease focussed approach with fewer side effects. Beyond depletion, tolerance induction therapies including Fc‑silenced anti‑CD3 antibodies such as teplizumab, promote functional silencing of autoreactive T cells. 

All of these therapies benefit from advances in Fc engineering. In particular, tuning antibodies to selectively engage the inhibitory Fc receptor, FcγRIIb, enhances agonistic signalling and Fc‑mediated functions while minimising off‑target inflammatory activity. Together, these innovations illustrate the broader shift toward mechanism‑guided interventions designed to restore immune balance without relying on broad immunosuppression

Multispecifics and T Cell Engagers (TCEs)

Multispecific biologics are expanding beyond oncology into autoimmunity, where their ability to precisely redirect or modulate immune cells offers new therapeutic angles. T cell–focused designs include bispecifics that inhibit autoreactive T cell activation by simultaneously blocking two costimulatory pathways or by bringing inhibitory receptors into closer proximity with their ligands to enforce tolerance. Re‑engineered T cell engagers aim to reshape the autoreactive pool more selectively, either by depleting pathogenic subsets or by redirecting them towards a more tolerogenic state. 

B cell–directed bispecifics have particularly strong traction given the central role of autoreactive B cells and their differentiation into antibody‑producing plasma cells. By combining markers such as CD19, CD20, or BCMA with inhibitory Fc‑modified scaffolds, these molecules can modulate pathogenic B cells and plasma cells while preserving broader humoral immunity. Combinations with T cells markers, such as CD3, can lead to depletion of broad B cells or specific subsets. Other approaches pair B cell antigens with tolerogenic receptors such as IL‑10R or TIGIT to push autoreactive clones toward anergy rather than deletion.

A major area of growth focuses on activating or expanding regulatory immune populations, especially regulatory T cells (Tregs). Multispecific cytokine or receptor‑targeted designs that co‑engage IL‑2 receptor subunits or pair IL‑2 variants with tissue‑homing cues are being explored to drive local, antigen‑specific tolerance. Similar strategies are being applied to regulatory B cells, tolerogenic dendritic cells, and select innate lymphoid populations. Overall, these platforms reflect a shift toward engineered, cell‑specific and context‑dependent immune retraining.

Small Molecules

Small‑molecule immunomodulators continue to evolve with greater target selectivity and improved benefit–risk profiles in autoimmunity. Many recent developments focus on kinase pathways central to lymphocyte activation, such as BTK, JAK, and TYK2. For example, Novartis’ oral BTK inhibitor remibrutinib is advancing across autoimmune indications including chronic spontaneous urticaria and multiple sclerosis, reflecting renewed interest in targeted oral agents. 

Alongside these late‑stage molecules, new early‑phase programs are expanding the small‑molecule space. Boehringer Ingelheim has recently licensed a first‑in‑class preclinical compound aimed at addressing unmet needs across inflammatory autoimmune diseases, underscoring industry commitment to next‑generation oral immunotherapies.

Evolving Assays: How RoukenBio is Engineering the Future of Autoimmune Testing

As the immunotherapy landscape continues its rapid shift toward autoimmunity, we have begun actively repurposing and redesigning our human‑relevant primary cell assays to meet the surge in demand for evaluating next‑generation autoimmune therapeutics. A selection of these is summarised below:  

T Cell Attenuation Assays

T cells are a major target of various therapeutics in autoimmunity but unlike I-O the intended outcome is attenuation of the response, not enhancement. This has required us to take a different approach to T cell functional assays; ensuring that we start with a high base response to provide a sufficient assay window for attenuation. Through our understanding of the underlying biology, we have been able to modify various assay setups including our one-way mixed-lymphocyte reaction (MLR)  as well as our in-house generated luminescent reporter assay to effectively demonstrate the capabilities of customer molecules to attenuate T cell responses. 

T Cell Depletion Assays

T cell depletion has emerged as an increasingly prominent strategy in recent years. The selective removal of antigen-specific T cells represents a promising method to eliminate disease-driving populations while minimising the risk of broad immunosuppression. Given that target populations are often limited in size, we have implemented a comprehensive approach to assay design to ensure effective evaluation of T cell depleting therapeutics. This includes primary cell assays assessing the viability of total or specific T cell subsets, isolation and expansion of target cells from PBMCs for cytotoxicity assays, and engineering cells to express the relevant target receptors. Together, these formats support precise assessment of therapeutic depletion, allowing developers to observe how efficiently individual T cell populations are targeted.

B Cell Depletion Assays

Originally developed for haematological malignancies, B cell depletion represents a promising therapeutic approach that is particularly appropriate for managing antibody-mediated autoimmune disorders. Current approaches span broad and targeted mechanisms, employing modalities such as T cell engagers and CAR‑T systems that eliminate pathogenic B cell populations with precision. Our whole PBMC and whole bone marrow mononuclear cells (BMMC) T cell dependent cellular cytotoxicity (TDCC) assays have been designed to accurate quantify depletion of healthy or disease-state whole and subset B cell populations. This assay design mitigates confounding factors such as TCE mediated epitope masking through a robust dual-marker strategy whilst our use of unfractionated PBMC or BMMC populations provides a physiologically relevant functional readout. 

Complementary assay formats further enable measurement of B cell marker expressing cell lines (e.g. CD19⁺ CHO cells) via impedance, ideal for evaluating CAR‑T therapeutics, and our reporter systems support assessment of antibody‑dependent cellular cytotoxicity (ADCC), antibody‑dependent cellular phagocytosis (ADCP), and complement‑dependent cytotoxicity (CDC), making them well suited for biosimilar screening and mechanistic characterisation.

Treg Suppression Assays

With interest in Treg biology accelerating across autoimmune pipelines, we have expanded our capabilities to isolate, expand, and functionally characterise both natural and inducible Treg populations. These protocols, optimised for donors with and without autoimmune disease, feed directly into our established suppression assay platform, enabling developers to observe how therapeutic candidates shape Treg differentiation, stability and suppressive potency. Flexible assay points, during expansion, induction, or direct co‑culture, ensure that nuanced modulatory effects can be captured with fidelity.

Tools & Resources 

Assay development at RoukenBio is aided by our access to the most effective tools and resources. Our in-house cell engineering team is an excellent resource capable of designing and generating custom cell lines that can be utilised in the design of new autoimmune assays. Services include gene design, expression control, knock-outs, knock-ins, knockdowns, TCR transgenic design and generation, reporter systems as well as the generation of cell therapies such as CAR-T cells. 

Additionally, with access to disease state PBMCs, bone marrow, plasma, serum and tissues we can tailor our assays to determine the impact of therapeutics on healthy and disease relevant material reflecting the biological complexity of real patient environments.

As therapeutic innovation in autoimmunity accelerates, we continue to extend our assay repertoire into more complex co‑cultures, 3D immune‑tissue systems, and early organoid‑based platforms. These emerging models are being shaped directly by the scientific advances and customer needs we encounter, ensuring our offerings evolve in step with the next generation of autoimmune research.

What's Next?

As RoukenBio continues to adapt to the accelerating shift toward autoimmune drug development, our expanding assay ecosystem positions us to support the next wave of mechanism‑driven therapeutics with the precision and physiological relevance they demand. What began as a repurposing of established I‑O assays has evolved into a broad, modality‑agnostic toolkit built around human primary cells, engineered systems and complex co‑cultures, each designed to illuminate the drivers of immune dysregulation with greater clarity. With customer demand rising across T cell, B cell, myeloid, Treg and antigen‑specific pathways, we remain committed to advancing the innovative in vitro approaches that will help shape the future of autoimmune therapy development.