Yale University

Other

Berger, Carole L.

Edelson, Richard Leslie

Carole L Berger

Richard L Edelson

Michael Girardi

Douglas Hanlon

Richard Leslie Edelson

Methods are provided for inducing differentiation of blood monocytes into functional antigen presenting dendritic cells. The blood monocytes are treated by exposing the monocytes to proteins adhered to the surface of a treatment device to induce differentiation of the monocytes in to dendritic cells. Differentiation of the monocytes may also be induced by physical perturbation of the monocytes during treatment. The treated monocytes may be co-incubated with disease effector agents, which may be phagocytized by the immature dendritic cells.

Methods for inducing the differentiation of blood monocytes into functional dendritic cells

Methods are provided for suppressing the immune system response in recipients of transplanted organs, tissues or cells. An extracorporeal quantity of blood from the intended transplant recipient is treated to induce monocytes contained in the blood to differentiate and form dendritic cells. The maturation of the dendritic cells is truncated at a stage where the dendritic cells can inactivate T cell clones which would otherwise generate an undesired immune system response. The immature dendritic cells can be directly administered to the transplant recipient, or the dendritic cells can be co-incubated with the bone marrow or stem cell preparation, prior to transplantation, in order to suppress or eliminate anti-recipient donor T cells contaminating the bone marrow or stem cell preparation. The methods can be used to suppress graft versus host disease in recipients of transplanted bone marrow or stem cells, or to suppress rejection of transplanted organs or tissue.

Method for suppressing immune system response to transplanted tissue or cells

A method for inducing differentiation of monocytes contained in an extracorporeal quantity of a subject's blood into functional dendritic antigen presenting cells is provided. The monocytes are induced to differentiate into dendritic cells by activation forces resulting from flow of the monocytes through a treatment apparatus having plastic channels. The interior surface of the plastic channel may be modified to increase the available surface area for interaction with blood monocytes. Platelets and serum protein may be removed from the blood prior to treatment to reduce or eliminate contamination of the plastic channel by these blood components. Functional dendritic cells generated from induced monocytes are incubated together with apoptotic or inactivated disease effector agents to enhance the presentation of at least one disease-causing antigen expressed by the disease effector agents. Compositions including dendritic cells derived from induced monocytes and compositions including such dendritic cells incubated with disease effector agents are also provided for use in immunotherapeutic treatment.

Methods for inducing the differentiation of monocytes into functional dendritic cells and immunotherapeutic compositions including such dendritic cells

A method for inducing differentiation of monocytes contained in an extracorporeal quantity of a subject's blood into functional dendritic antigen presenting cells is provided. The monocytes are first treated by exposure to physical perturbation, irradiation in the presence of a photoactivatable agent capable of forming photoadducts with cellular DNA components, and/or treatment with a DNA binding agent. The treated monocytes are then incubated for a period of time sufficient to maximize the number of functional dendritic cells in the treated cell population. Functional dendritic cells generated from induced monocytes are incubated together with disease effector agents to enhance the presentation of at least one disease-causing antigen expressed by the disease effector agents.

Growing community of inventors

Bronx, NY, United States of America

Carole L Berger