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Histopathologic, phenotypic, and molecular criteria to discriminate low-grade intestinal T-cell lymphoma in cats from lymphoplasmacytic enteritis

Posted by Nicole
Differentiation of low-grade intestinal T-cell lymphoma (LGITL) from lymphoplasmacytic enteritis (LPE) in cats is a diagnostic challenge for pathologists.
Characterize histologic, Bio Med Frontiers immunohistochemical, and molecular features of LGITL and LPE.
 Forty-four client-owned cats, 22 diagnosed with LGITL and 22 with LPE.
Prospective, cohort study. Clinical suspicion of LGITL or LPE was based on persistent gastrointestinal signs, unresponsive to empirical treatments. All cats underwent a standardized diagnostic evaluation, including biopsy (preferentially full-thickness), and were diagnosed with LGITL or LPE after review of clinical, laboratory, sonographic, histologic, immunohistochemical, and clonality results.
 A monomorphic lymphocytic population (22/22, 100%) and in-depth mucosal infiltration (15/22, 68%) were hallmarks of LGITL.
Epithelial patterns (nests and plaques) were significantly more frequent in LGITL (11/22, 50%) than in LPE (1/22, 5%) cases (P = .001). A CD3+ lymphocytic apical-to-basal gradient was observed in 9/22 (41%) of LGITL vs 1/22 (5%) of LPE cases (P = .004). Most LPE cases (17/18, 94%) featured marked fibrosis in the superficial part of the lamina propria. The Ki-67 20%- and 30%-thresholds discriminated between LGITL and LPE within both the epithelium (specificity >95%) and lamina propria (specificity >95%), respectively.
All LGITL cases were CD3+ pSTAT3- and pSTAT5+. T-cell receptor gamma chain gene rearrangements indicated monoclonality in 86% of LGITL cases. Surprisingly, 70% of LPE cases featured monoclonality (40%) or monoclonality on a polyclonal background (30%).
We identified new histologic, immunohistochemical, and clonality criteria to distinguish LGITL from LPE.
 CD20; CD3; JAK-STAT; Ki-67; PARR; alimentary lymphoma; clonality; epithelium; fibrosis; full-thickness intestinal biopsies; gradient; histology; immunohistochemistry; inflammatory bowel disease; lamina propria; monoclonal; nest; plaque; polyclonal.

PAX8 lineage-driven T cell engaging antibody for the treatment of high-grade serous ovarian cancer.

High-grade serous ovarian cancers (HGSOC) represent the most common subtype of ovarian malignancies. Due to Learn More the frequency of late-stage diagnosis and high rates of recurrence following standard of care treatments, novel therapies are needed to promote durable responses.
We investigated the anti-tumor activity of CD3 T cell engaging bispecific antibodies (TCBs) directed against the PAX8 lineage-driven HGSOC tumor antigen LYPD1 and demonstrated that anti-LYPD1 TCBs induce T cell activation and promote in vivo tumor growth inhibition in LYPD1-expressing HGSOC.
To selectively target LYPD1-expressing tumor cells with high expression while sparing cells with low expression, we coupled bivalent low-affinity anti-LYPD1 antigen-binding fragments (Fabs) with the anti-CD3 scFv.
In contrast to the monovalent anti-LYPD1 high-affinity TCB (VHP354), the bivalent low-affinity anti-LYPD1 TCB (QZC131) demonstrated antigen density-dependent selectivity and showed tolerability in cynomolgus monkeys at the maximum dose tested of 3 mg/kg.
Collectively, these data demonstrate that bivalent TCBs directed against LYPD1 have compelling efficacy and safety profiles to support its use as a treatment for high-grade serous ovarian cancers.

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