Novel anti-CD30/CD3 bispecific antibodies activate human T cells and mediate potent anti-tumor activity

CD30 is expressed on Hodgkin lymphomas (HL), many non-Hodgkin lymphomas (NHLs), and non-lymphoid malignancies in children and adults. Tumor expression, combined with restricted expression in healthy tissues, identifies CD30 as a promising immunotherapy target. An anti-CD30 antibody-drug conjugate (ADC) has been approved by the FDA for HL. While anti-CD30 ADCs and chimeric antigen receptors (CARs) have shown promise, their shortcomings and toxicities suggest that alternative treatments are needed. We developed novel anti-CD30 x anti-CD3 bispecific antibodies (biAbs) to coat activated patient T cells (ATCs) ex vivo prior to autologous re-infusions. Our goal is to harness the dual specificity of the biAb, the power of cellular therapy, and the safety of non-genetically modified autologous T cell infusions. We present a comprehensive characterization of the CD30 binding and tumor cell killing properties of these biAbs. Five unique murine monoclonal antibodies (mAbs) were generated against the extracellular domain of human CD30. Resultant anti-CD30 mAbs were purified and screened for binding specificity, affinity, and epitope recognition. Two lead mAb candidates with unique sequences and CD30 binding clusters that differ from the ADC in clinical use were identified. These mAbs were chemically conjugated with OKT3 (an anti-CD3 mAb). ATCs were armed and evaluated in vitro for binding, cytokine production, and cytotoxicity against tumor lines and then in vivo for tumor cell killing. Our lead mAb was subcloned to make a Master Cell Bank (MCB) and screened for binding against a library of human cell surface proteins. Only huCD30 was bound. These studies support a clinical trial in development employing ex vivo-loading of autologous T cells with this novel biAb

Maize Conzi Has Distinct Patterns of Expression in Different Photoperiods and Confers Photoperiod Sensitivity in Rice

Flowering is a critical transition in the life cycle of Angiosperms. The cycle begins with seed germination and continues as the plant produces vegetative structures such as leaves during its juvenile stage of growth. As the plant becomes competent to reproduce, it enters the adult stage of vegetative growth. Finally the plant begins reproductive growth and flowers which, if fertilization is successful, leads to the production of seed. Plants devote a great deal of resources to reproductive growth and seed production to provide the best possible chances for the success of the progeny. Because flowering is such a critical step in development, once this transition is initiated it typically cannot be reversed. Plants monitor and respond to many conditions, both endogenous and environmental, such that reproduction is stimulated when conditions are optimal..

Maize Conzi has Distinct Patterns of Expression in Different Photoperiods and Confers Photoperiod Sensitivity in Rice

Flowering is a critical transition in the life cycle of Angiosperms. The cycle begins with seed germination and continues as the plant produces vegetative structures such as leaves during its juvenile stage of growth. As the plant becomes competent to reproduce, it enters the adult stage of vegetative growth. Finally the plant begins reproductive growth and flowers which, if fertilization is successful, leads to the production of seed. Plants devote a great deal of resources to reproductive growth and seed production to provide the best possible chances for the success of the progeny. Because flowering is such a critical step in development, once this transition is initiated it typically cannot be reversed. Plants monitor and respond to many conditions, both endogenous and environmental, such that reproduction is stimulated when conditions are optimal..