Inhaled therapeutics have high potential for the treatment of chronic respiratory diseases of high unmet medical need, such as idiopathic pulmonary fibrosis (IPF). Preclinical and early clinical evidence show that cellular communication network factor 2 (CCN2), previously called connective tissue growth factor (CTGF), is a promising target for the treatment of IPF. In recent phase 3 clinical trials, however, systemic CCN2 inhibition failed to demonstrate a clinically meaningful benefit. Here, we present the preclinical profile of the inhaled anti-CCN2 Anticalin® protein PRS-220. Our study demonstrates that efficient pulmonary delivery directly translates into superior efficacy in relevant models of pulmonary fibrosis when compared to systemic CCN2 inhibition. Moreover, we present a holistic approach for the preclinical characterization of inhaled PRS-220 from state-of-the art in vitro and in vivo models to novel human ex vivo and in silico models, highlighting the advantage of inhaled drug delivery for treatment of respiratory disease.

IOMX-0675 is a monoclonal immunoglobulin G1 (IgG1) antibody targeting LILRB1 (ILT2) and LILRB2 (ILT4), key immunosuppressive receptors of the leukocyte immunoglobulin-like receptor (LILR) family, that play a pivotal role in tumor immune evasion. LILRB1 and LILRB2 recognize both classical and non-classical MHC-I molecules and are highly expressed on tumor-infiltrating myeloid cells, with LILRB1 also found on lymphoid cells. Their frequently observed upregulation in patients non-responsive to T cell checkpoint blockade, implicate a role in driving tumor resistance. Expression profiling revealed co-expression of immune-activating LILR members, LILRA1 and LILRA3, with LILRB1 and LILRB2 in specific cancer indications, underscoring the importance of selective receptor targeting to achieve effective therapeutic outcomes. IOMX-0675, identified through iOmx’s proprietary phage display library, exhibits a highly differentiated binding profile with selective, high-affinity binding to the inhibitory receptors LILRB1 and LILRB2, while showing only weak affinity to the closely related immune-activating LILR family members LILRA1 and LILRA3. In autologous immune cell co-cultures, IOMX-0675 effectively reprograms immunosuppressive macrophages in a dose-dependent manner, restoring lymphoid immune cell function. Importantly, IOMX-0675 retains its high selectivity for LILRB1 and LILRB2 and its pharmacodynamic activity, even in environments dominated by LILRA1 and LILRA3. IOMX-0675 enhances phagocytic activity, stimulates pro-inflammatory functions across various macrophage subtypes and drives robust pro-inflammatory cytokine secretion in stimulated PBMCs, both in vitro and in ex vivo whole blood assays. In a CD34+ stem cell-engrafted humanized mouse melanoma model, IOMX-0675 exhibited potent anti-tumor activity and repolarized tumor-associated macrophages, closely aligning with in vitro findings and underscoring its therapeutic promise. In summary, we developed IOMX-0675, a highly selective cross-specific antibody that effectively antagonizes both LILRB1 and LILRB2 while exhibiting negligible binding to immune-activating LILR family members. IOMX-0675 demonstrates robust reprogramming of the immunosuppressive myeloid compartment and restores cytotoxic T cell activity within the tumor microenvironment, both in vitro and in vivo. Its differentiated binding profile positions IOMX-0675 as a best-in-class therapeutic candidate with the potential to maximize anti-tumor efficacy and address significant unmet medical needs for patients. Kristina Heinig, Christina A. Hartl, Marisa Stebegg-Wagner, Eugenia Korotkova, Michail Maraslis, Carmen Ginzel, Thomas Jaquin, Bettina Langer, Jonas Schilz, Alina Huth, Maximilian Aigner, Alexander N. Marziale, Stefan Bissinger. IOMX-0675, a LILRB1/LILRB2 cross-specific antibody that repolarizes the tumor microenvironment to drive potent anti-tumor activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2237.

Severe asthma is a syndromic label assigned to patients based on clinical parameters, yet there are diverse underlying molecular endotypes in severe asthma pathobiology. Immunophenotyping of asthma biospecimens commonly includes a mixture of granulocytes and lymphocytes. Recently, a subset of patients with severe asthma was defined as non-type 2 with neutrophil-enriched inflammation associated with increased Th17 CD4+ T cells and IL-17 levels. Here, we used an allergen-driven mouse model of increased IL-17 and mixed granulocyte lung inflammation to determine the impact of upstream regulation by an Anticalin protein that specifically binds IL-23. Airway administration of the IL-23-binding Anticalin protein (AcIL-23) decreased lung neutrophils, eosinophils, macrophages, lymphocytes, IL-17+ CD4 T cells, mucous cell metaplasia, and methacholine-induced airway hyperresponsiveness. Selective targeting of IL-23 with a monoclonal antibody (IL-23p19; αIL-23) also decreased macrophages, IL-17+ CD4 T cells, and airway hyperresponsiveness. In contrast, a monoclonal antibody against IL-17A (αIL-17A) had no significant effect on airway hyperresponsiveness but did decrease lung neutrophils, macrophages, and IL-17+ CD4 T cells. Targeting the IL-23 pathway did not significantly change IL-5+ or IL-13+ CD4 T cells. Together, these data indicate that airway AcIL-23 mirrored the activity of systemic anti-IL-23 antibody to decrease airway hyperresponsiveness in addition to mixed granulocytic inflammation and that these protective actions were broader than blocking IL-17A or IL-5 alone, which selectively decreased airway neutrophils and eosinophils, respectively.NEW & NOTEWORTHY This is the first report of an Anticalin protein engineered to neutralize IL-23 (AcIL-23). Airway administration of AcIL-23 in mice regulated allergen-driven airway inflammation, mucous cell metaplasia, and methacholine-induced airway hyperresponsiveness. In mixed granulocytic allergic lung inflammation, immune regulation of IL-23 was broader than neutralization of either IL-17 or IL-5.

Mucus hypersecretion and mucus obstruction are pathogenic features in many chronic lung diseases directly linked to disease severity, exacerbation, progression, and mortality. The Jagged-1/Notch pathway is a promising therapeutic target that regulates secretory and ciliated cell trans-differentiation in the lung. However, the Notch pathway is also required in various other organs. Hence, pulmonary delivery of therapeutic agents is a promising approach to target this pathway while minimizing systemic exposure. Using Anticalin technology, Jagged-1 Anticalin binding proteins were generated and engineered to potent and selective inhalable Jagged-1 antagonists. Their therapeutic potential to reduce airway mucus hyperproduction and obstruction was investigated ex vivo and in vivo. In primary airway cell cultures grown at an air-liquid interface and stimulated with inflammatory cytokines, Jagged-1 Anticalin binding proteins reduced both mucin gene expression and mucous cell metaplasia. In vivo, prophylactic and therapeutic treatment with a pulmonary-delivered Jagged-1 Anticalin binding protein reduced mucous cell metaplasia, epithelial thickening, and airway mucus hyperproduction in IL-13 and house dust mite allergen-challenged mice, respectively. Furthermore, in a transgenic mouse model with pathophysiologic features of cystic fibrosis and chronic obstructive pulmonary disease (COPD), pulmonary-delivered Jagged-1 Anticalin binding protein reduced hallmarks of airway mucus obstruction. In all in vivo models, a reduction of mucous cells with a concomitant increase of ciliated cells was observed. Collectively, these findings support Jagged-1 antagonists' therapeutic potential for patients with muco-obstructive lung diseases and the feasibility of targeting the Jagged-1/Notch pathway by inhalation.NEW & NOTEWORTHY Airway mucus drives severity and mortality in diverse chronic lung diseases. The Jagged-1/Notch pathway controls the balance of ciliated versus mucous cells, but targeting the pathway systemically carries the risk of side effects. Here we developed novel, Anticalin-derived, pulmonary-delivered Jagged-1 antagonists, to inhibit airway mucus hyperproduction and obstruction in chronic lung diseases. Our preclinical data demonstrate the effectiveness of these antagonists in diminishing secretory cell and mucus levels and alleviating hallmarks of mucus obstruction.

Background: PRS-344/S095012 is a novel 4-1BB (CD137) and programmed death-ligand 1 (PD-L1) bispecific antibody-Anticalin® fusion protein (MabcalinTM protein) designed to cluster 4-1BB on activated T cells exclusively in the presence of PD-L1 expressing cells. We aimed to study PRS-344/S095012 in vivo biodistribution and pharmacokinetics with 89Zr-positron emission tomography (PET) at a dose with antitumoral activity in mice and evaluate the contribution of each targeting arm. Methods: PRS-344/S095012 lacks cross-reactivity to murine 4-1BB and PD-L1. To explore the PRS-344/S095012 biodistribution in a humanized 4-1BB knock-in mouse model, we synthesized the surrogate 89Zr-Atezo-J10 with the same 4-1BB building block and cross-reactivity to murine PD-L1. Humanized 4-1BB knock-in C57BL/6J (h4-1BB KI B6) and C57BL/6J (B6) mice (n=4-6 per group) were subcutaneously engrafted with murine wildtype MC38 colon adenocarcinoma cells. Tumors were grown to a minimum of ≥50 mm3 (average 163 mm3) before tracer injection. Mice received intravenously 30 µg (2.5 MBq) of 89Zr-PRS-344/S095012 or 89Zr-Atezo-J10 supplemented with PRS-344/S095012 or Atezo-J10 up to 10 mg/kg. Four mice groups were formed to distinguish between bispecific (Atezo-J10 in h4-1BB KI B6), monospecific PD-L1 (Atezo-J10 in B6), monospecific 4-1BB (PRS-344/S095012 in h4-1BB KI B6), and isotype (PRS-344/S095012 in B6) binding up to 4 days post-injection (pi). In addition, a fifth group (5 MBq 89Zr-Atezo-J10) was studied to visualize the bispecific biodistribution up to 7 days pi. At days 1, 2, 4, or 2, 4, 7 pi, mice underwent serial PET imaging to obtain mean and maximum standardized uptake (SUVmean/max) and retro-orbital blood sampling, followed by ex vivo biodistribution. Results: PET imaging showed 89Zr-Atezo-J10 specific tumor accumulation with higher tumor-to-blood ratios of respectively 2.2-, 2.6-, and 2.4-fold (p<0.01) at 4 days pi compared to monospecific binding of PD-L1, 4-1BB, and isotype. The ex vivo biodistribution demonstrated the same trend with respectively 4.2-, 5.5-, and 6.8-fold (p<0.01) increase in tumor-to-blood uptake for 89Zr-Atezo-J10 versus monospecific binding of PD-L1, 4-1BB, and isotype 89Zr-Atezo-J10 spleen uptake was comparable (ns) with monospecific binding of PD-L1 but elevated (p<0.01) compared to 4-1BB or isotype distribution. The uptake in lymph nodes (axillary, cervical, tumor-draining, and mesenteric) did not differ between the groups. Conclusion: 89Zr-Atezo-J10 specific accumulation in PD-L1 expressing tumors is due to both PD-L1 and 4-1BB binding and is higher than with PD-L1 and 4-1BB mono-targeting. This preclinical study supports the clinical evaluation of 89Zr-PRS-344/S095012’s whole-body distribution and the development of tumor-specific 4-1BB targeting bispecifics. Citation Format: Claudia A. van Winkel, Xiaoyu Fan, Danique Giesen, Glenn Gauderat, Lucia Pattarini, Thomas Jaquin, Anissa Barakat, Anne-Marie De La Bigne, Marleen Richter, Nicole Andersen, Julie Legrand, Helene Lelièvre, Elisabeth G. de Vries, Aizea Morales-Kastresana, Marjolijn N. Lub- de Hooge. Assessment of target-mediated biodistribution of an 89Zr labeled PD-L1/4-1BB bispecific Mabcalin protein. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3579.

Supplementary Figure from The PD-L1/4-1BB Bispecific Antibody–Anticalin Fusion Protein PRS-344/S095012 Elicits Strong T-Cell Stimulation in a Tumor-Localized Manner

Background: Inhaled drug delivery is a promising approach in drug development for treating respiratory diseases. Anticalin® proteins are a unique class of inhalable biotherapeutics, whose favorable biophysical properties and small size (~20 kDa) support administration via inhalation. PRS-220 is an inhalable Anticalin protein targeting CTGF in development as a novel therapy for fibrotic lung disease including IPF. Objective: We investigate the nebulization performance and in vivo lung biodistribution of PRS-220 to characterize its profile for inhaled lung delivery. Methods: The behavior and integrity of PRS-220 upon nebulization was characterized by state-of-the-art protein analytical methods and aerosol analyses, including next generation impactor analysis. Mucus interaction was measured in vitro. The pharmacokinetic profile of PRS-220 was analyzed upon lung delivery in rodents. The lung biodistribution profile of fluorescently labeled PRS-220 in fibrotic mouse lungs was investigated by 3D light sheet imaging of whole lungs and 2D confocal microscopy. Results: Aerosolized PRS-220 shows aerodynamic properties suitable for effective lung deposition. Favorable biophysical properties allow PRS-220 to retain stability upon nebulization and prevent its interaction with mucus. Lung PK analyses confirm an advantageous profile, including high exposure in the lung and low systemic exposure. PRS-220 shows a beneficial lung tissue distribution profile in fibrotic mouse lungs by penetrating the alveolar compartment and fibrotic lung interstitium. Conclusion: The excellent properties for inhaled lung delivery make PRS-220 a promising treatment option for IPF.

AbstractPurpose: While patients responding to checkpoint blockade often achieve remarkable clinical responses, there is still significant unmet need due to resistant or refractory tumors. A combination of checkpoint blockade with further T-cell stimulation mediated by 4-1BB agonism may increase response rates and durability of response. A bispecific molecule that blocks the programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis and localizes 4-1BB costimulation to a PD-L1–positive (PD-L1+) tumor microenvironment (TME) or tumor draining lymph nodes could maximize antitumor immunity and increase the therapeutic window beyond what has been reported for anti–4-1BB mAbs. Experimental Design: We generated and characterized the PD-L1/4-1BB bispecific molecule PRS-344/S095012 for target binding and functional activity in multiple relevant in vitro assays. Transgenic mice expressing human 4-1BB were transplanted with human PD-L1–expressing murine MC38 cells to assess in vivo antitumoral activity. Results: PRS-344/S095012 bound to its targets with high affinity and efficiently blocked the PD-1/PD-L1 pathway, and PRS-344/S095012-mediated 4-1BB costimulation was strictly PD-L1 dependent. We demonstrated a synergistic effect of both pathways on T-cell stimulation with the bispecific PRS-344/S095012 being more potent than the combination of mAbs. PRS-344/S095012 augmented CD4-positive (CD4+) and CD8-positive (CD8+) T-cell effector functions and enhanced antigen-specific T-cell stimulation. Finally, PRS-344/S095012 demonstrated strong antitumoral efficacy in an anti–PD-L1–resistant mouse model in which soluble 4-1BB was detected as an early marker for 4-1BB agonist activity. Conclusions: The PD-L1/4-1BB bispecific PRS-344/S095012 efficiently combines checkpoint blockade with a tumor-localized 4-1BB–mediated stimulation burst to antigen-specific T cells, more potent than the combination of mAbs, supporting the advancement of PRS-344/S095012 toward clinical development. See related commentary by Shu et al., p. 3182

Background: Anticalin® proteins derived from human lipocalins can be engineered to bind to their targets with high potency and selectivity and are well-suited for inhaled delivery with the potential for a higher therapeutic index. The Jagged-1/Notch pathway is a promising therapeutic target given preclinical data reflecting its role in goblet cell metaplasia and mucus obstruction that are pathogenic features of many chronic airway diseases. Objective: To develop a Jagged-1-binding Anticalin protein for the treatment of muco-obstructive lung diseases via an inhaled delivery. Methods: Display selection technology was used for candidate identification. Binding characteristics and in vitro potency of Jagged-1-targeting Anticalin proteins were determined. Anticalin proteins were screened for their ability to interact with the mucus layer. The impact of Jagged-1-binding Anticalin proteins was assessed in primary human bronchial epithelial cell (HBEC) air-liquid-interface (ALI) cultures. Results: We identified Anticalin proteins binding with high affinity and specificity to different epitopes of Jagged-1. Further, a dose-dependent inhibition of Jagged-1-Notch2 interaction was observed. Jagged-1-targeting Anticalin proteins reduced secretory- and increased ciliated cell marker expression in ex vivo HBEC ALI cultures and showed little or no interaction with mucus to ensure target engagement. Conclusions: We report the identification of novel and potent Jagged-1-targeting Anticalin proteins. The data support further development of PRS-400 as a potential inhaled therapy for patients with muco-obstructive respiratory diseases.

Aims and objectives: CTGF (CCN2), a secreted matricellular protein, has been identified as a mediator of fibrosis. First clinical validation of this target in IPF has been provided by positive results of a systemically-delivered antibody in Phase 2 clinical studies. Anticalin® proteins derived from human lipocalins can be engineered to bind to their targets with high potency and selectivity, similar to antibodies. Based on their biophysical properties, Anticalin proteins are well suited for lung delivery as demonstrated by the inhaled PRS-060/AZD1402, currently in Phase 2 studies for asthma. Here we describe the development of PRS-220, an Anticalin-based CTGF inhibitor, for treatment of IPF via inhalation. Methods: Phage display selection of Anticalin libraries was used for initial candidate identification and optimization. Binding characteristics of CTGF-targeting Anticalin proteins were determined using protein and cell-based assays. The PK profile and in vivo potency of CTGF-binding Anticalin proteins upon lung delivery were assessed in healthy and bleomycin-challenged mice. Results: We identified Anticalin proteins binding to different epitopes of CTGF with picomolar affinities. Target engagement was confirmed with CTGF-expressing, TGF-β1-stimulated primary human lung fibroblasts. Lung delivery of CTGF-targeting Anticalin proteins in bleomycin-challenged mice attenuated fibrotic lung remodeling in vivo. Conclusion: Here we report the identification of a novel class of high affinity CTGF inhibitors for treatment of IPF using the Anticalin technology. The preclinical and developability data support further development of PRS-220 as a potential best-in-class inhaled IPF therapy.

The therapeutic utility of systemic “biologicals” (i.e. recombinant proteins), in particular monoclonal antibodies, has rekindled interest in development of diverse inhaled biological platforms to treat lung diseases. However, very little is known about the specific patterns and mechanisms of their uptake, epithelial transfer, clearance and redistribution. Here we compare conventional PK analysis with whole-of-lung biodistribution by 3D light-sheet microscopy (LSM) and FACS profiling of macrophages using a human NGAL lipocalin protein as a test probe. Methods: Unlabelled NGAL was microsprayed into male Balb/c mice lungs. At 1, 2, 4, 6, & 24h, blood, PBS lung washes and lung lobes were collected. Separately, fluoro tagged NGAL-647 was microsprayed into mouse lungs, harvested, optically cleared and imaged by LSM and lung macrophages analysed by FACS. Results: Instilled NGAL displayed first order elimination kinetics. Appeared in the blood in a dose proportional manner (Tmax=2h,& Cmax=1859 ng/ml). LSM confirmed progressive redistribution from the airway lumen into the interstitium; most likely by paracellular transport. As previously demonstrated, instilled protein macrophage uptake was inferred from a punctate cell biodistribution pattern and redistribution at later time points. This was confirmed by FACS as the majority of NGAL+ cells were alveolar monocyte/macrophages cells. Conclusion: Consistent with previous reports, NGAL delivered directly to the lung by microspray undergoes first order elimination, transit from lumen to submucosa in airways and lumen to interstitium and blood from the alveoli as well as macrophage uptake and clearance via the mucociliary escalator.

IPF is a progressive and lethal disease and phase 2 trials have shown that inhibition of CTGF (Pamrevlumab/FG3019, Fibrogen Inc.) or Autotaxin (Ziretaxestat/GLPG1690 Galapagos Inc.) slow the decline in FVC experienced by IPF patients. Given the stabilization of FVC observed from combining Nintedanib and Pirfenidone, we investigated the potential benefit of combining FG3019 and GLPG1690 in a mouse model of IPF. Mice were subjected to intratracheal dosing of bleomycin to induce lung fibrosis and treated with FG3019 and/or GLPG1690 for 14 days. Changes in bodymass, survival, physiological measurements, plasma, BALF and lung tissue were recorded during the study. The progression of fibrosis was determined by Flexivent, lung hydroxyproline levels, Ashcroft-Hubner histopathological scores, as well as machine learning-based of lung sections or micro CT-scanned lungs respectively. FG3019 prevented the increase in lung hydroxyproline levels caused by bleomycin, while treatment with GLPG1690 did not have this effect. In contrast, GLPG1690 treated mice had better FVC and inspiratory capacity than vehicle controls, while mice receiving FG3019 did not. The combination of FG3019 and GLPG1690 reduced the accumulation of lung hydroxyproline and improved lung function parameters. The Ashcroft-Hubner scores were reduced in mice receiving FG3019 or GLPG1690 as a single treatment, but further reductions were not observed mice treated with FG3019 and GLPG1690. The combination of FG3019 and GLPG1690 treatment demonstrated an enhanced therapeutic efficacy by conferring the independent and parallel benefits of the single agents on experimental lung fibrosis endpoints.

Background. Preclinical and clinical data suggest that 4-1BB (CD137), a costimulatory immunoreceptor mainly expressed by cytotoxic cells, represents a promising therapeutic target in cancer. A combination of checkpoint blockade with further T-cell activation mediated by 4-1BB co-stimulation may increase response rates and durability of response. However, the efficacy of systemic 4-1BB stimulation is limited by on target peripheral toxicity events. PRS-344/S095012 has been designed to provide the potential of a combinatorial therapy in one molecule and favor the localized stimulation of antigen-specific T cells in the tumor microenvironment, potentially reducing peripheral toxicity. Methods. Anticalin® proteins are 18 kDa protein therapeutics derived from human lipocalins. We utilized phage display technologies to generate an Anticalin protein that binds to 4-1BB with high affinity and specificity. PRS-344/S095012 was generated by recombinant fusion of two 4-1BB-specific Anticalin proteins to a PD-L1-targeting monoclonal antibody with a modified IgG4 backbone that avoids interaction with Fc gamma receptors and restricts 4-1BB agonism to PD-L1 positive tissues. The activity and potency of PRS-344/S095012 were investigated in binding assays, functional in vitro assays with human primary immune cells, as well as in a human 4-1BB knock in mouse model. Results. The bispecific fusion protein PRS-344/S095012 is capable of binding 4-1BB and PD-L1 simultaneously. We show that the bispecific compound retains its ability to block PD-1/PD-L1 receptor-ligand interaction with similar potency to the parental PD-L1 antibody. In relevant in vitro cell-based assays, PRS-344/S095012 enhances T cell effector functions only in the presence of PD-L1 positive cells, in line with the desired mechanism of action. In vitro, we show that PRS-344/S095012 activity is superior to PD-L1 antibodies, and to the combination of clinically relevant 4-1BB and PD-L1 benchmark antibodies. In a human 4-1BB knock in mouse model, subcutaneously implanted with a human PD-L1 expressing tumor, PRS-344/S095012 showed clear superiority to anti-PD-L1 alone and a robust antitumor response that leads to the complete regression of implanted tumors and extension of survival. Conclusion. We report potent costimulatory T cell engagement of the immunoreceptor 4-1BB in a PD-L1-dependent manner, utilizing the PD-L1/4-1BB bispecific compound PRS-344/S095012. This approach has the potential to provide a localized costimulation of the immune system with high efficacy and reduced peripheral toxicity. Furthermore, dual mechanism of action combining PD-L1-dependent 4-1BB agonist activity with simultaneous PD-1/PD-L1 pathway blockade provides an additional therapeutic benefit in preclinical models. Taken together our in vitro and in vivo data outlines proof of concept functionality of PRS-344/S095012 and supports further development of this promising compound. Citation Format: Aizea Morales-Kastresana, Marina Pavlidou, Janet Peper, Lucia Pattarini, Christian Barthels, Eva-Maria Hansbauer, Rachida Bel Aiba, Birgit Bossenmaier, Alix Scholer-Dahirel, Thomas Jaquin, Catherine Gallou, Veronique Blanc, Christine Rothe, Shane Olwill. Simultaneous costimulatory T-cell engagement and checkpoint inhibition by PRS-344/S095012, a PD-L1/4-1BB bispecific compound for tumor localized activation of the immune system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB135.