Iryna Vasyliv

All Publications

• B7-H4 ImmunoPET Imaging Tracks Tumor-Associated Macrophage Changes in Prostate Cancer. Molecular pharmaceutics Kumar, M., Singh, S. B., Vasyliv, I., Habte, F., Kalita, M., Alam, I. S., Koladiya, A., Dai, S. Y., James, M., Rao, J., Beziere, N., Daldrup-Link, H. E. 2025

  Abstract

  B7-H4 is an inhibitory immune checkpoint molecule that is upregulated in various cancers and correlates with advanced tumor stages and poor clinical outcomes. This study aimed to develop an immunoPET radiotracer for noninvasive assessment of B7-H4 expression in tumors and tumor-associated macrophages (TAM) and to evaluate the radiotracer potential to monitor therapeutic responses. We generated a B7-H4-targeted immunoPET imaging tracer by radiolabeling the anti-B7-H4 monoclonal antibody (2H9) with [89Zr], yielding [89Zr]Zr-DFO-2H9, and assessed its biodistribution in prostate cancer xenografts to quantitatively measure B7-H4 expression in vivo. In vitro binding studies confirmed the retained immunoreactivity and specificity for B7-H4. Radiochemical purity was verified using size exclusion chromatography. In vivo evaluation of [89Zr]Zr-DFO-2H9 was first performed in immunodeficient nude mice bearing subcutaneous DU145 human prostate tumors, with longitudinal PET imaging conducted over 7 days postinjection, followed by terminal biodistribution analysis. [89Zr]Zr-DFO-2H9 demonstrated a good tumor-binding profile and specificity in DU145 tumor xenografts. To distinguish PET signals from tumor cells versus macrophages, immunocompetent C57BL/6 mice bearing syngeneic TRAMP-C2 prostate tumors were divided into three cohorts and treated with PBS (control), cold anti-B7-H4 mAb (for B7-H4 blockade), or clodronate liposome (for macrophage depletion). In TRAMP-C2 tumors, the PET signal was significantly reduced in both the B7-H4 blocked and macrophage-depleted group compared to controls. Immunohistochemistry revealed that B7-H4 expression differences among TRAMP-C2 treatment groups were not as clearly distinguishable as those observed in vivo via PET imaging. Multiplexed immunofluorescence staining of macrophage markers indicated that infiltrating TAMs were the major contributors to B7-H4-specific PET signals within the tumor stroma. Collectively, these results show that [89Zr]Zr-DFO-2H9 binds B7-H4 with high affinity and specificity and reflects changes in TAM levels in vivo. The new radiotracer shows promise for detecting B7-H4 positive tumors and TAM levels, profiling the immune microenvironment, and monitoring macrophage-targeted immunotherapies.

  View details for DOI 10.1021/acs.molpharmaceut.5c00637

  View details for PubMedID 41122911

• Impact of CAR T cell therapy on thymus size in children and young adults with acute lymphoblastic leukemia. Scientific reports Vasyliv, I., Kim, H. G., Erickson, C., Baggott, C., Schultz, L. M., Liang, T., Ramakrishna, S., Devis, K. L., Daldrup-Link, H. E. 2025; 15 (1): 30360

  Abstract

  Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated efficacy in children and young adult patients with acute lymphoblastic leukemia (ALL). The purpose of our study was to investigate thymus size changes after CAR T-cell therapy, explore the associated clinical conditions, and assess survival differences of patients who underwent CAR T-cell therapy, we conducted a single-center retrospective study of children and young adult patients who underwent CAR T-cell therapy for ALL between April 2015 and October 2023.We measured the volume of the thymus on pre- and post-CAR T-cell chest CT scans of 20 patients (median [IQR] age, 18[11] years; 11 females). We divided patients into two groups, those who did (group 1) or did not (group 2) demonstrate increase in thymus size after therapy. Clinical and survival data were collected. We used the Wilcoxon signed-rank test or Fisher's exact test for group comparisons and analyzed event-free survival data. Seven of 20 patients (35%, group 1) showed increase in thymus volume (pre- vs. post-CAR T-cell thymus volume; 5.01 [2.18] cm³ vs. 20.87 [19.86] cm³, p = 0.01), while 13 patients (65%, group 2) showed no increase in thymus volume (pre- vs. post-CAR T-cell thymus volume; 3.01 [13.42] cm³ vs. 2.09 [8.34] cm³, p = 0.01). Patients in group 1 were younger (12 [8] years vs. 19[10] years, p = 0.028) and showed a higher rate of event-free survival compared to those in group 2 (p = 0.003). In children and young adults with ALL, increased thymus size after CAR T-cell therapy was associated with younger age and improved clinical outcomes.

  View details for DOI 10.1038/s41598-025-12630-2

  View details for PubMedID 40830378

  View details for PubMedCentralID PMC12365290

• MRI detection of senescent cells in porcine knee joints with a β-galactosidase responsive Gd-chelate. Npj imaging Nernekli, K., Mangarova, D. B., Suryadevara, V., Hajipour, M., Tang, J. H., Wang, J., Liang, T., Harris, M., Ueyama, T., Lyons, J. K., Moseley, M. E., Roudi, R., Pisani, L., von Krüchten, R., Duwa, R., Lu-Liang, S. Y., Shokri Varniab, Z., Vasyliv, I., Das, N., Murayama, M., Shinohara, I., Pratx, G., Goodman, S. B., Meade, T. J., Daldrup-Link, H. E. 2025; 3 (1): 18

  Abstract

  Senescent cells promote osteoarthritis progression through the secretion of inflammatory mediators. Preclinical studies have identified senescence-associated beta-galactosidase (β-gal) as a biomarker of senescence, but in vivo detection remains challenging. Here, we evaluated whether a β-gal responsive gadolinium (Gd) chelate can non-invasively detect β-gal expressing senescent cells with standard clinical magnetic resonance imaging (MRI) technology in vitro, ex vivo, and in vivo in porcine joints. In vitro studies showed that senescent mesenchymal stromal cells (MSCs) exhibited significant MRI signal enhancement upon incubation with the β-gal responsive Gd-chelate compared to viable control cells. In vivo, intraarticular injection of the probe into pig knee joints revealed its retention and activation by senescent cells in cartilage defects, evidenced by a significant increase in R 1 relaxation rate. MRI-based senescent cell detection holds promise for identifying patients amenable to senolytic therapies, tailoring treatment plans, and monitoring therapy response in real-time.

  View details for DOI 10.1038/s44303-025-00078-y

  View details for PubMedID 40330124

  View details for PubMedCentralID PMC12049270

• Brain MRI changes in children and young adults with B-cell acute lymphoblastic leukemia following chimeric antigen receptor T-cell therapy. European radiology Kim, H. G., Yeom, K. W., Vasyliv, I., Shokri Varniab, Z., Erickson, C., Baggott, C., Schultz, L. M., Daldrup-Link, H. E. 2025

  Abstract

  To evaluate brain MRI findings in children and young adults after chimeric antigen receptor (CAR) T-cell therapy for B-cell acute lymphoid leukemia (B-ALL) and associate results with clinical and neurological symptoms.We reviewed pre- and post-CAR-T cell therapy brain MRIs of B-ALL patients aged 25 years or younger who underwent therapy between April 2015 and October 2023 at a single institution. MRI abnormalities were categorized as no change, exacerbation of preexisting lesion, or newly developed lesion. Clinical CAR-mediated toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) grades, were recorded. Patients were grouped into those with and without 'exacerbated/new lesion,' and clinical and neurological symptoms were compared using Fisher's exact test.Sixteen patients with pre- and post-CAR brain MRIs (median age 16 years [interquartile range, 11-21]; 9 males, 7 females) were included in the analysis. Post-CAR brain abnormalities were observed in 81% (13/16) of patients, including white matter (WM) signal changes (12/16), leptomeningeal enhancement (1/16), and cerebellar embolic infarction (1/16). Of the post-CAR WM lesions, 50% (6/12) were exacerbated, 33% (4/12) were newly developed, and 17% (2/12) remained unchanged compared to pre-CAR brain MRI. No difference in CRS (p = 0.079) or ICANS grades (p > 0.99) was observed between patients with and without 'exacerbated/new lesions'.Children and young adults with B-ALL can develop brain MRI abnormalities after CAR T-cell therapy, predominantly WM signal changes. These brain abnormalities did not show an association with higher CRS or ICANS grade.Question Brain MRI findings after chimeric antigen receptor (CAR) T-cell therapy for B-cell acute lymphoid leukemia (B-ALL) and their association with clinical and neurological symptoms are not well understood. Findings Brain MRI abnormalities, mostly white matter changes, were seen in 81% of patients but were not associated with CAR-mediated toxicities. Clinical relevance Brain MRI abnormalities, commonly observed post-CAR T-cell therapy, do not correlate with the severity of CAR-related toxicities, aiding in the clinical management and monitoring of these patients.

  View details for DOI 10.1007/s00330-025-11515-2

  View details for PubMedID 40111490

  View details for PubMedCentralID 4058440

• Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial. ESMO open Michels, S., Massutí, B., Vasyliv, I., Stratmann, J., Frank, J., Adams, A., Felip, E., Grohé, C., Rodriguez-Abreu, D., Bischoff, H., Carcereny I Costa, E., Corral, J., Pereira, E., Fassunke, J., Fischer, R. N., Insa, A., Koleczko, S., Nogova, L., Reck, M., Reutter, T., Riedel, R., Schaufler, D., Scheffler, M., Weisthoff, M., Provencio, M., Merkelbach-Bruse, S., Hellmich, M., Sebastian, M., Büttner, R., Persigehl, T., Rosell, R., Wolf, J. 2024; 9 (2): 102237

  Abstract

  In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we present the final analysis of OS, systemic and intracranial activity, and the impact of co-occurring aberrations.EUCROSS was a prospective, single-arm, phase II trial. The primary endpoint was best overall response rate (ORR) using RECIST 1.1. Secondary and exploratory endpoints were progression-free survival (PFS), OS, and efficacy in pre-defined subgroups.Median OS of the intention-to-treat population (N = 34) was 54.8 months [95% confidence interval (CI) 20.3 months-not reached (NR); median follow-up 81.4 months] and median all-cause PFS of the response-evaluable population (N = 30) was 19.4 months (95% CI 10.1-32.2 months). Time on treatment was significantly correlated with OS (R = 0.82; P < 0.0001). Patients with co-occurring TP53 aberrations (28%) had a significantly shorter OS [hazard ratio (HR) 11; 95% CI 2.0-56.0; P = 0.006] and all-cause PFS (HR 4.2; 95% CI 1.2-15; P = 0.025). Patients with central nervous system (CNS) involvement at baseline (N = 6; 20%) had a numerically shorter median OS and all-cause PFS. Median intracranial PFS was 32.2 months (95% CI 23.7 months-NR) and the rate of isolated CNS progression was 24%.Our final analysis proves the efficacy of crizotinib in ROS1-positive lung cancer, but also highlights the devastating impact of TP53 mutations on survival and treatment efficacy. Additionally, our data show that CNS disease control is durable and the risk of CNS progression while on crizotinib treatment is low.

  View details for DOI 10.1016/j.esmoop.2024.102237

  View details for PubMedID 38350336

  View details for PubMedCentralID PMC10937203