Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma

Antibody engineering can tailor the design and activities of therapeutic antibodies for better efficiency or other advantageous clinical properties. Here we report the development of ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies. ISB 1442 consists of two anti-CD38 arms targeting two distinct epitopes that preferentially drive binding to tumor cells and enable avidity-induced blocking of proximal CD47 receptors on the same cell while preventing on-target off-tumor binding on healthy cells. The Fc portion of ISB 1442 is engineered to enhance complement dependent cytotoxicity, antibody dependent cell cytotoxicity and antibody dependent cell phagocytosis. ISB 1442 thus represents a CD47-BsAb combining biparatopic targeting of a tumor associated antigen with engineered enhancement of antibody effector function to overcome potential resistance mechanisms that hamper treatment of myeloma with monospecific anti-CD38 antibodies. ISB 1442 is currently in a Phase I clinical trial in relapsed refractory multiple myeloma

Numerical and experimental investigations of damping of flax-epoxy laminated composite

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Role of interface formation versus fibres properties in the mechanical behaviour of bio-based composites manufactured by Liquid Composite Molding processes

The aim of this work was to study the effect of free surface energy modification of flax fibres by a thermal treatment on the mechanical behaviour of bio-based composites. It has been proved that this modification enhances the wettability of flax fibres by liquid epoxy resin and results in a lower porosity amount in composites. Tests to evaluate mechanical properties of elementary fibres, yarns and composites have been performed. The main outcome of this multiscale study, even if elementary fibres and yarns have been embrittled and interface properties have been lowered after thermal treatment, is that the mechanical behaviour of composites manufactured by Liquid Composite Molding (LCM) is better with treated fibres

Experimental and numerical investigation of the damping of flax–epoxy composite plates

International audienceIn this paper, the vibration behaviour and damping performances of Flax Fiber Reinforced Epoxy (FFRE) are investigated. Static tests using FFRE composite beams are carried out leading to the identification of elastic properties of each layer. Then, three FFRE composite plates are elaborated and used in experimental vibration tests to identify their eigenfrequencies and their modal damping. In numerical part, a constant complex representation of the stiffness is assumed and the loss factors are supposed constants and identified from the first experimental vibration mode. The homogenization technique and the finite element method are applied to describe their damped dynamic behaviour. The resolution of the resulting non-linear problem is carried out using the Asymptotic Numerical Method (ANM). Experimental results show that the modal damping is greater when the flax fibers are oriented at 90°. Comparing numerical and experimental results, the proposed finite element modelling enables to estimate the damped eigenfrequencies with high accuracy. However, the predicted modal loss factors are over-estimated compared to experimental ones. It is concluded that the present modelling should be improved considering the frequency dependence of damping

Impregnated fibre bundle test for natural fibres used in composites

International audienceIn this study, the impregnated fibre bundle test, a common method used by carbon and glass fibre manufacturers to determine the properties of fibres used in composites, was adapted for natural fibres and validated by a round robin test on one type of natural fibres, namely flax fibres. Five European laboratories have carried out in parallel the impregnated fibre bundle test, on the same batch of hackled flax (long fibres), to check the applicability and reliability of this modified method on natural fibres. The results were compared to the more traditional single fibre test on elementary fibres. The back-calculated fibre stiffness shows a very low scatter between the five laboratories of less than +/- 5% (59.8 +/- 2.4 GPa, as measured between 0 and 0.1% strain). The fibre ultimate tensile strength of 527 +/- 138 MPa has a higher scatter, compared to stiffness values, as this property is highly sensitive to imperfections and flaws

Impregnated fibre bundle test for natural fibres used in composites

In this study, the impregnated fibre bundle test, a common method used by carbon and glass fibre manufacturers to determine the properties of fibres used in composites, was adapted for natural fibres and validated by a round robin test on one type of natural fibres, namely flax fibres. Five European laboratories have carried out in parallel the impregnated fibre bundle test, on the same batch of hackled flax (long fibres), to check the applicability and reliability of this modified method on natural fibres. The results were compared to the more traditional single fibre test on elementary fibres. The back-calculated fibre stiffness shows a very low scatter between the five laboratories of less than ±5% (59.8 ± 2.4 GPa, as measured between 0 and 0.1% strain). The fibre ultimate tensile strength of 527 ± 138 MPa has a higher scatter, compared to stiffness values, as this property is highly sensitive to imperfections and flaws.status: publishe

Impregnated fibre bundle test for natural fibres used in composites

International audienceIn this study, the impregnated fibre bundle test, a common method used by carbon and glass fibre manufacturers to determine the properties of fibres used in composites, was adapted for natural fibres and validated by a round robin test on one type of natural fibres, namely flax fibres. Five European laboratories have carried out in parallel the impregnated fibre bundle test, on the same batch of hackled flax (long fibres), to check the applicability and reliability of this modified method on natural fibres. The results were compared to the more traditional single fibre test on elementary fibres. The back-calculated fibre stiffness shows a very low scatter between the five laboratories of less than +/- 5% (59.8 +/- 2.4 GPa, as measured between 0 and 0.1% strain). The fibre ultimate tensile strength of 527 +/- 138 MPa has a higher scatter, compared to stiffness values, as this property is highly sensitive to imperfections and flaws

Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma

Abstract Antibody engineering can tailor the design and activities of therapeutic antibodies for better efficiency or other advantageous clinical properties. Here we report the development of ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies. ISB 1442 consists of two anti-CD38 arms targeting two distinct epitopes that preferentially drive binding to tumor cells and enable avidity-induced blocking of proximal CD47 receptors on the same cell while preventing on-target off-tumor binding on healthy cells. The Fc portion of ISB 1442 is engineered to enhance complement dependent cytotoxicity, antibody dependent cell cytotoxicity and antibody dependent cell phagocytosis. ISB 1442 thus represents a CD47-BsAb combining biparatopic targeting of a tumor associated antigen with engineered enhancement of antibody effector function to overcome potential resistance mechanisms that hamper treatment of myeloma with monospecific anti-CD38 antibodies. ISB 1442 is currently in a Phase I clinical trial in relapsed refractory multiple myeloma

Development of ISB 1442, a CD38 and CD47 bispecific biparatopic antibody innate cell modulator for the treatment of multiple myeloma

Antibody engineering can tailor the design and activities of therapeutic antibodies for better efficiency or other advantageous clinical properties. Here we report the development of ISB 1442, a fully human bispecific antibody designed to re-establish synthetic immunity in CD38+ hematological malignancies. ISB 1442 consists of two anti-CD38 arms targeting two distinct epitopes that preferentially drive binding to tumor cells and enable avidity-induced blocking of proximal CD47 receptors on the same cell while preventing on-target off-tumor binding on healthy cells. The Fc portion of ISB 1442 is engineered to enhance complement dependent cytotoxicity, antibody dependent cell cytotoxicity and antibody dependent cell phagocytosis. ISB 1442 thus represents a CD47-BsAb combining biparatopic targeting of a tumor associated antigen with engineered enhancement of antibody effector function to overcome potential resistance mechanisms that hamper treatment of myeloma with monospecific anti-CD38 antibodies. ISB 1442 is currently in a Phase I clinical trial in relapsed refractory multiple myeloma