Purpose: Radiotherapy modifies the tumor microenvironment and causes the release of tumor antigens, which can enhance the effect of immunotherapy. L19 targets the extra domain B (ED-B) of fibronectin, a marker for tumor neoangiogenesis, and can be used as immunocytokine when coupled to IL2. We hypothesize that radiotherapy in combination with L19-IL2 provides an enhanced antitumor effect, which is dependent on ED-B expression.Experimental Design: Mice were injected with syngeneic C51 colon carcinoma, Lewis lung carcinoma (LLC), or 4T1 mammary carcinoma cells. Tumor growth delay, underlying immunologic parameters, and treatment toxicity were evaluated after singledose local tumor irradiation and systemic administration of L19-IL2 or equimolar controls.Results: ED-B expression was high, intermediate, and low for C51, LLC, and 4T1, respectively. The combination therapy showed (i) a long-lasting synergistic effect for the C51 model with 75% of tumors being cured, (ii) an additive effect for the LLC model, and (iii) no effect for the 4T1 model. The combination treatment resulted in a significantly increased cytotoxic (CD8 þ

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IntroductionAn increased risk of vertebral fracture (VF) is one of the extra-articular manifestations of spondyloarthropathy (SpA). The prevalence of moderate to severe VFs visualized by radiography (Rx) in patients with SpA in daily practice is unknown until imaging of the full spine is available, as most VFs do not present with clinical signs and symptoms of an acute fracture.MethodsWe evaluated the prevalence of VFs (>25 % loss in height) on available Rx and dual-energy X-ray absorptiometry (DXA) images in 390 consecutive patients with SpA in daily practice. We assessed their association with disease characteristics, bone mineral density, the modified Stoke Ankylosing Spondylitis Spinal Score, and history of trauma.ResultsForty-six patients (11.8 %) had Rx VF (56.4 % men, 93.5 % in the thoracic spine), and 44.5 % had multiple VFs. Compared with patients without VF, patients with VF were older (52.2 vs. 47.3 years, p < 0.01; range 25–84 years), had lower femoral neck T-scores (−1.1 vs. −0.7; p < 0.05), and had a marginally higher modified Stoke Ankylosing Spondylitis Spinal Score (11.7 vs. 7.0; p = 0.06). Among patients with VFs, 15.2 % had a history of trauma with acute back pain (p < 0.001 vs. no VF). The reliability of DXA for diagnosing radiographic VFs was high (κ 0.90).ConclusionsModerate to severe VFs are found in more than 10 % of patients with SpA before the age of 40 years in 5 % of women and 9 % in men. Most VFs are located in the thoracic region, are related to low femoral neck bone mineral density and to stiffening of the spine, and are only rarely related to trauma history. DXA is a useful alternative for diagnosing VFs.

Objective This study was undertaken to identify novel autoantibodies in axial spondyloarthritis (SpA) and determine their diagnostic potential in patients with early axial SpA and controls from 2 independent cohorts. Methods An axial SpA complementary DNA phage display library was used to screen for novel IgG antibodies in plasma from patients with early axial SpA. The presence of these antibodies against novel peptides (i.e., peptides identified in an early axial SpA cohort from Hasselt University, designated UH‐axSpA) was determined by enzyme‐linked immunosorbent assay in 76 patients with early axial SpA, 75 controls with nonspecific chronic low back pain, 60 patients with rheumatoid arthritis, and 94 healthy controls from the UH cohort. Antibody reactivity to these novel peptides was further validated in 174 patients with axial SpA (of whom 79 had early axial SpA) from the University Hospitals Leuven (Bio)SPAR (Spondyloarthritis [Biologics]) cohort. Results We identified antibodies to 9 novel UH‐axSpA peptides, corresponding to randomly formed peptides and to a novel axial SpA autoantigen, double homeobox protein 4. Antibodies to 3 UH‐axSpA peptides with the highest positive likelihood ratio (LR) for a diagnosis of axial SpA were present in significantly more patients with early axial SpA from the UH and (Bio)SPAR cohorts (14.2% [22/155]) compared to controls with chronic low back pain (5% [4/75]), resulting in 95% specificity. The positive LR for confirming axial SpA using antibodies to these 3 UH‐axSpA peptides was 2.7, which is higher than the LR obtained with the currently used laboratory marker C‐reactive protein. Testing for antibodies to these 3 UH‐axSpA peptides in patients with chronic low back pain increased the posttest probability of a diagnosis of axial SpA from 79% to 91%. Conclusion Antibodies to 3 UH‐axSpA peptides could provide a novel tool in the diagnosis of a subset of axial SpA patients.

<div>Abstract<p><b>Purpose:</b> Radiotherapy modifies the tumor microenvironment and causes the release of tumor antigens, which can enhance the effect of immunotherapy. L19 targets the extra domain B (ED-B) of fibronectin, a marker for tumor neoangiogenesis, and can be used as immunocytokine when coupled to IL2. We hypothesize that radiotherapy in combination with L19-IL2 provides an enhanced antitumor effect, which is dependent on ED-B expression.</p><p><b>Experimental Design:</b> Mice were injected with syngeneic C51 colon carcinoma, Lewis lung carcinoma (LLC), or 4T1 mammary carcinoma cells. Tumor growth delay, underlying immunologic parameters, and treatment toxicity were evaluated after single-dose local tumor irradiation and systemic administration of L19-IL2 or equimolar controls.</p><p><b>Results:</b> ED-B expression was high, intermediate, and low for C51, LLC, and 4T1, respectively. The combination therapy showed (i) a long-lasting synergistic effect for the C51 model with 75% of tumors being cured, (ii) an additive effect for the LLC model, and (iii) no effect for the 4T1 model. The combination treatment resulted in a significantly increased cytotoxic (CD8⁺) T-cell population for both C51 and LLC. Depletion of CD8⁺ T cells abolished the benefit of the combination therapy.</p><p><b>Conclusions:</b> These data provide the first evidence for an increased therapeutic potential by combining radiotherapy with L19-IL2 in ED-B–positive tumors. This new opportunity in cancer treatment will be investigated in a phase I clinical study for patients with an oligometastatic solid tumor (NCT02086721). An animation summarizing our results is available at <a href="https://www.youtube.com/watch?v=xHbwQuCTkRc" target="_blank">https://www.youtube.com/watch?v=xHbwQuCTkRc</a>. <i>Clin Cancer Res; 21(5); 1151–60. ©2014 AACR</i>.</p></div>