Biology subjects

Kabha, M.

Publications and source records attributed to Kabha, M..

2 recordsLinked to original sources

bioRxiv2026

Human Sperm-Induced Cell-Cell Fusion Requiring JUNO (hSPICER): A paradigm shift to test sperm fertilizing potential

Current evaluation of male fertility is largely based on indirect sperm parameters such as viability, concentration, morphology, and motility; however, each of these parameters, alone or combined, has been shown to have limited predictive value for successful fertilization. To address this problem, we introduce hSPICER (human SPerm-Induced CEll-cell fusion Requiring JUNO), an assay that evaluates sperm function based on their ability to induce fusion of somatic cells expressing human JUNO (hJUNO), the egg-specific sperm receptor. Similarly to our previous discovery in mice, we found that human sperm can fuse with somatic cells expressing hJUNO on their surface (pseudo-eggs) and promote content mixing between cells in culture, as measured using a split GFP system. The assay is sensitive, specific, and species-dependent, requiring hJUNO for optimal signal. We generated a stable cell line expressing hJUNO, enhancing reproducibility and sensitivity. We also show that hSPICER is compatible with cryopreserved sperm and consistent over different days. Importantly, hSPICER values correlate with fertilization outcomes of patients during fertility treatments, indicating its potential as a functional diagnostic tool. Beyond diagnostic uses, hSPICER establishes a platform to explore sperm fusion mechanisms and to screen for therapeutic compounds and interventions to treat low fertility, enhance fertilization, and develop non-hormonal contraceptives for males and females, as well as quality assessment of semen samples in fertility clinics and sperm banks.

developmental biology↗

bioRxiv2025

An Aged Microenvironment Increases CAR T Cell Cytotoxicity but Impairs Therapeutic Efficacy

BackgroundCancer disproportionately affects the elderly, who are often less able to tolerate traditional cytotoxic therapies, and may benefit from T cell-based immunotherapies. However, studies evaluating the efficacy of T cell immunotherapy in aged mice are limited and yield inconsistent results, while clinical data are largely retrospective. MethodsHere, we used a murine model of Chimeric Antigen Receptor (CAR) T cell therapy to investigate how aging influences efficacy, from CAR T cell production to in vivo anti-tumor activity. ResultsWe found that aging reduced CAR T cell production yields and altered their phenotype and function. Aged CAR T cells were predominantly effector memory CD4 T cells, whereas young CAR T cells were primarily central memory CD8 T cells. Functionally, aged CAR T cells exhibited non-specific cytotoxicity, driven by constitutive degranulation and elevated granzyme B secretion independent of CAR expression. This phenotype was induced by the aged microenvironment, as young T cells transferred into aged hosts adopted similar behavior. In vivo, young CAR T cells efficiently reduced tumor burden in young leukemia-bearing hosts, but were not effective in aged hosts, where the aged microenvironment impaired CAR T cell persistence. ConclusionThese findings indicate that aging impacts CAR T cell therapy at multiple levels, from manufacturing to therapeutic efficacy, highlighting the need to design tailored immunotherapies for elderly patients.

immunology↗